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Ann Thorac Surg 1996;61:252-258
© 1996 The Society of Thoracic Surgeons

Current Review

The Dendritic Cell Lineage: A Ubiquitous Antigen-Presenting Organization

Gilbert Massard, MD, Marie-Marthe Tongio, MD, Jean-Marie Wihlm, MD, Georges Morand, MD

Department of Thoracic Surgery, University Hospital of Strasbourg, and Tissue Typing Laboratory, Centre Régional de Transfusion Sanguine, Strasbourg, France


   Abstract
Top
 Footnotes
 Abstract
Introduction
 Common Characteristics of the...
 Particular Implications Within...
 Conclusion
 References
 
Dendritic cells are specialized antigen-presenting cells with two unique characteristics: the greatest stimulatory potential and the ability to stimulate naive T-lymphocytes. They originate from the bone marrow and reach their destination via hematogenous or lymphatic migration. Their phenotype is characterized by a high expression of major histocompatibility complex class II molecules and a high expression of adhesion molecules (CD25, CD54, CD58, CD72, and CD80). Pulmonary dendritic cells may be investigated by histologic examination, phenotype analysis, and function studies in a mixed lymphocyte reaction. Their isolation requires enzymatic digestion of lung tissue and subsequent steps of cell separation. The complexity of these manipulations makes it difficult to obtain large numbers of viable cells. A close anatomic relationship with alveolar macrophages underlines a functional interconnection: macrophages down-regulate the antigen-presenting function through release of tumor necrosis factor {alpha}. Dendritic cells most probably play a major role in lung diseases such as histiocytosis, primary and secondary cancers, and both acute and chronic lung graft rejection. Identification of the precise functional pathways might lead to therapeutic use of modulation of dendritic cell function.


   Introduction
Top
 Footnotes
 Abstract
 Introduction
Common Characteristics of the...
 Particular Implications Within...
 Conclusion
 References
 
Host immune response to a foreign antigen is initiated and effected by T lymphocytes. Because T lymphocytes are unable to directly recognize a foreign antigen, an obligatory step of antigen presentation by specialized accessory cells, called antigen-presenting cells (APCs), is required. Although various leukocytes, such as B lymphocytes, monocytes, and macrophages, may operate as APCs, a particular lineage specifically devoted to antigen presentation has been identified. These specialized APCs are called dendritic cells (DCs), because of their morphology. They form a ubiquitous system, and their presence has been described in most tissues according to histologic studies. Functionally speaking, DCs differ from other APCs by two major characteristics. First, DCs are the most potent stimulator cells of T lymphocytes: stimulation is 10 to 100 times greater with DCs than with any other APC. Second, DCs are the only APC able to present novel antigens to naive T lymphocytes and to promote an immune response [1–3]. The paramount importance of DCs in any immune reaction suggests that a clearer understanding of DC function might open the way to improved management of many chest diseases. Dendritic cells probably interfere in the genesis of many chronic lung diseases, be it allergies, primary or secondary tumors, infections, or interstitial diseases. The still disappointing long-term results observed after lung transplantation will hopefully be improved owing to more precise identification of the mechanisms of acute and chronic rejection, which are certainly initiated by DCs. The purpose of the present article is to review up-to-date knowledge on DCs in general, and to give some insight into the various aspects that have been investigated and are still topics of ongoing research regarding DCs within the lung.

As an opening remark, we should point out that the ideas presented in this article have been selected according to the scientific credit given to the senior authors of the referenced publications. However, any experimental fact has been observed under very particular experimental conditions and should not be extrapolated to different specific conditions. On the other hand, a review article would not be readable if every experimental condition were to be reported. Because comparison of isolated experimental data is subjected to some confusion and misinterpretation, we suggest that the interested reader go back to the referenced article to complete his or her information.


   Common Characteristics of the Dendritic Cell Lineage
Top
 Footnotes
 Abstract
 Introduction
 Common Characteristics of the...
Particular Implications Within...
 Conclusion
 References
 
Most of the current knowledge concerning human DCs has been acquired by research studies made with specimens of skin or peripheral blood, which are both easy to obtain and to manipulate. However, DCs have been further identified in most organs and tissues. The main varieties are the cutaneous Langerhans cell, the circulating DC of the peripheral blood, the lymphatic veiled cell, and the digitated cell of the spleen and lymph nodes [2, 3]. Dendritic cells have been observed in the thymus, in the colon, in the synovia, in the peritoneum, and in the lung [4–7]. In the lung, a high presence of DCs is anticipated, given that several antigens are inhaled constantly [8]. However, isolation of DCs is subject to considerable impediments. Dendritic cells have no specific surface markers of their own (except cutaneous Langerhans cells, which express the CD1a molecule); therefore, their isolation requires step-by-step depletion of other, readily identifiable populations of leukocytes. The number of cells recovered after separations is generally quite low and hence narrows the spectrum of possible investigations. Further, the phenotype of DCs may change during culture, and these changes may even be enhanced through release of various cytokines during manipulations or cell lysis. All these reasons explain the slow progress, as well as the sometimes controversial results.

Origin of Dendritic Cells
Dendritic cells have a common progenitor cell together with the monocyte-macrophage lineage, because both express the medullary antigens CD33 and CD34 [2, 3, 9]. Further, bone marrow cultures sampled from patients recovering from aplasia after chemotherapy grow both lineages spontaneously [10]. However, there is a lack of consensus whether the dendritic and monocyte-macrophage lineages are really distinct, or whether they represent two different functional states of the same cell lineage. Steinman [3] argues for a distinct dendritic lineage, because DCs do not express any macrophage-monocyte marker. Thus, it appeared with CD34+ precursor cells isolated from umbilical cord blood that differentiation might be directed toward the macrophage lineage with granulocyte-macrophage colony stimulating factor (GM-CSF), and toward the DC-lineage with tumor necrosis factor {alpha} [11, 12]. In contrast, the fact that DCs have been obtained from cultures of CD14+ cells, presumed to be purified monocytes, argues for a common lineage. Under specific in vitro conditions, monocytes shed their specific CD14 marker and increase the expression of major histocompatibility complex (MHC) class II molecules [13, 14]. The humoral mediators for this metamorphosis of monocytes to DCs are mainly interleukin-4 (IL-4) and IL-13. The effect of IL-4 is amplified with GM-CSF, and antagonized by interferon {gamma} [15]. Interleukin-13 further increases survival of monocytes in culture [15, 16].

Migration of Dendritic Cells
The ubiquitous distribution of DCs all over the organism requires migration patterns leading the DCs from their medullary origin via the blood or lymphatic stream to sites of antigen uptake and subsequently to lymphoid effector organs. The sites of antigen uptake are most likely epithelial surfaces such as skin, bronchi, alveoli, or bowel, whereas the effector organs are lymphatic organs containing T cells. Besides well-delimited lymphoid organs such as thymus, nodes, and spleen, the gut-associated lymphoid tissue and the bronchus-associated lymphoid tissue are possible sites of antigen presentation. As a matter of fact, experimental studies have identified two different migration pathways. A hematogenous migration directed toward the spleen has been illustrated in a murine model. Isotopically labeled splenic DCs have been injected intravenously: the cells first migrated to the lung, where a short sequestration of about 1 hour occurred; a secondary migration then happened toward the liver, and finally to the spleen. However, these intravenously injected cells were unable to penetrate lymphatic nodes, even after splenectomy [17]. Similarly, in a rat cardiac allograft model, donor DCs migrated to the spleen [18].

On the other hand, splenic DCs injected subcutaneously migrated toward the paracortical region of the draining lymph nodes [19, 20]. The latter example illustrates the pathway of migration generally accepted for cutaneous Langerhans cells: these cells at first internalize antigens in the skin, and subsequently migrate to the lymph nodes, where they present the antigen to T lymphocytes [19]. Comparably, splenic DCs injected intratracheally migrate to the mediastinal nodes, and intraperitonerally injected DCs migrate to the mesenteric nodes [20, 21].

Phenotype of Dendritic Cells and Its Changes During Culture
As one may expect with respect to the antigen-presenting function, DCs strongly express molecules involved with antigen presentation and T-cell activation on their cytoplasmic membrane: these are mainly the MHC class II molecules on the one hand, and a variety of adhesion molecules on the other hand. After contact with T cells, the density of adhesion molecules is even enhanced [22]. However, DCs consistently lack the monocyte marker CD14. The expression of immunoglobulin receptors is controversial. Controversy regarding particular aspects of the phenotype is not surprising because it appears that the phenotype may change during culture. For example, native, freshly isolated cutaneous Langerhans cells only moderately express MHC class II molecules, and are recognized owing to a high expression of CD1a; in addition, they are positive for the Fc receptor CD32. After some days in culture, the expressions of CD1a and CD32 disappear. The expression of both MHC class II and class I molecules is intensified, and various activation and adhesion molecules appear: IL-2 receptor (CD25), LFA-3 (CD58), and ICAM-1 (CD54) [23]. Comparable findings have been demonstrated with peripheral blood DCs [24], with the restriction that blood DCs do not express the CD1a molecule. The explanation for this maturation is probably that the function of native DCs is to internalize and process antigens toward a presentable state; as a matter of fact, native cells are weak stimulators in a mixed lymphocyte reaction. While antigen processing is achieved, the phenotype matures for effective T-cell activation. The main mediator of this maturation seems to be GM-CSF, which prolongs viability of Langerhans cells or peripheral blood DCs in vitro and amplifies their accessory activity [25]. Tumor necrosis factor {alpha}, on the other hand, only prolongs viability [26, 27]. Lymphatic DCs of the rat mature by a combined activity of GM-CSF and IL-1ß [28].

Activation of T Cells
Dendritic cells are capable of inducing an immune response in naive T lymphocytes, which have never been in contact with a given antigen. The T-cell subtype in immediate contact with DCs are the T helper cells, recognized by the CD4 molecule, although the cytotoxic T cells or CD8 might be directly activated by DCs. According to the precise function of CD4 cells, we distinguish two subtypes: the Th1 cell, which induces type IV cellular immune reactions, and the Th2 cell, which initiates humoral immune response [29]. The common pathway of antigen presentation is the MHC molecule. If a foreign MHC class II is directly recognized, ie, if a foreign DC is in contact with a self T cell, one speaks about direct presentation. Indirect presentation occurs when a self DC presents with its MHC class II a foreign peptide to self T cells. Both mechanisms may lead to acute allograft rejection [30]. The contact between APC and T cell is established through adhesion of the MHC class II molecule and the T-cell receptor complex CD3, completed by the coreceptor CD4. However, this single contact between MHC class II molecule and T-cell receptor is not sufficient to trigger an immune response, and a second signal is required. Although it was formerly believed that this second signal was mediated by cytokines such as IL-1 or IL-6 secreted at the time of contact [31], there is increasing evidence that this signal is initiated by the linkage of various intercellular adhesion molecules. The most prominent couples that have been identified to date are summarized in Table 1Go [32].


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  		Table 1. . Adhesion Molecules Interfering With T-Cell Activation
 
Expression of adhesion molecules such as CD80, CD54, and CD58 is increased after contact with T cells. The CD28-CD80 couple is considered most important [33]. In vitro, activation of purified T cells may be achieved by stimulation with either anti-CD3 or anti-CD28 antibodies. Cyclosporine may inhibit activation with anti-CD3, but not with anti-CD28 antibodies [34, 35]. The common final pathway of T-cell activation is IL-2 secretion. Single CD3 activation leads to an unstable messenger RNA for IL-2, whereas CD28 stimulation leads to a very stable messenger RNA synthesis [33]. On the other hand, VCAM-1 (vascular cell adhesion molecule), whose ligand on T cells is VLA-4 (very late activation antigen, CD49d/CD29), has only been identified on the follicular DC subset [36, 37]. Like E-selectin (binding to L-selectin on T cells), it is merely a molecule expressed by activated endothelial cells [37]. The most important adhesion molecules for lung DCs seem to be LFA-2 (CD2), LFA-3 (CD58), and ß-integrins (CD18 : CD11c, CD29) [38, 39].

Lack of the second signal leads to absence of immune response, and probably to tolerance. Induction of allograft tolerance through blockade of the CD48-CD2 couple has been achieved in a murine heart transplant model [40].


   Particular Implications Within the Lung
Top
 Footnotes
 Abstract
 Introduction
 Common Characteristics of the...
 Particular Implications Within...
Conclusion
 References
 
Methods of Investigation
Approaches to pulmonary DCs may rely on histologic techniques, phenotype analysis, or functional studies.

Histologic examination provides information on the relations of DCs with neighbor cells within the general architecture of bronchial or pulmonary tissue. Previous investigations have shown DCs within the bronchi, peripheral lung, and pleura in histologic preparations. In these experiments, DCs were recognized through revealing of the S-100 protein, which is also contained in neuroglial cells [41]. More recent studies have relied on immunohistochemical identification of the HLA-DR molecule [7]. Fresh DCs may also be identified by staining of the cytoplasmic CD68 content; this molecule is spread all over the cytoplasm in macrophages, and forms typical perinuclear spots in DCs [42]. Frozen tissues and cytospin preparations may further be stained with anti-CD1a and anti-CD1c antibodies [43]. Observation of bronchial DCs should ideally be made on tangential sections [44].

Both analysis of the phenotype and function studies require previous preparation of a cell suspension. This is achieved with enzymatic digestion of peripheral lung tissue, and subsequent cell separations [45–47]. Deletion of T lymphocytes, macrophages, B lymphocytes, and natural killer cells may be obtained either on physical grounds (adhesion for macrophages, sheep red cell rosetting for T lymphocytes, density gradient for B lymphocytes) or in a more sophisticated manner with cell sorting on a flow cytometer. Because no specific marker for DCs is available, a negative selection has to be made: known leukocytes (eg, T lymphocytes, macrophages) are labeled, and unlabeled cells are selected [24]. Cells with a low autofluorescence might be primarily DCs [48, 49].

The phenotype may be detailed with monoclonal antibody labeling either on cytospin preparations or with flow cytometry. Flow cytometry, however, requires a large number of cells (at least 250,000 per antibody), and retrieval of cells after several manipulations results quite often in a small number of cells.

Function of DCs is assessed in a mixed lymphocyte reaction. There are two types of reaction that are currently used. Direct antigen presentation is tested in an allogenic model, where stimulating DCs are cultured with allogenic responding peripheral blood mononuclear cells or peripheral blood lymphocytes. Indirect presentation is simulated in an autogenic model, where stimulating DCs present a soluble antigen (eg, ovalbumin) to presensitized autogenic lymphocytes [48, 49].

Origin of Pulmonary Dendritic Cells
The immunologic incompetence of the bronchial mucosa in newborns is correlated to an absence of APC in the fetal or newborn bronchial mucosa. In rodents, a progressive colonization of the tracheobronchial mucosa with DCs occurring during the time span between birth and weaning has been documented [50]. There seems to be a precursor cell that does not express the MHC class II molecules. These cells acquire the class II expression progressively during the neonatal period. At the same time, antigen-presenting cells appear in the alveolar tissue. This colonization is accelerated by interferon {gamma} and antagonized by aerosolized steroids [50].

Histology
Pulmonary DCs are mainly located in the airway mucosa and in the alveolar septa. Airway DCs are located either in close contact to the basal membrane with their digitations floating in the lumen or in the submucosa close to serous acini [7, 51]. The morphologic features of bronchial DCs are similar in mice, rats, and humans. Distribution of these cells is variable according to the level of the bronchial tree, and decreases considerably below the third generation of bronchi: the concentration is greater than 600 cells/mm2 at the tracheal level and less than 300 cells/mm2 below the third generation of bronchi [44]. When local inflammation occurs, the number of DCs increases, and the number and size of dendrites increase as well; the phenotype changes toward an increased expression of adhesion molecules (in particular CD11a:CD18) [44]. Alveolar DCs are mainly located in the alveolar septa, close to the areas of septal fusion. A possible interaction between alveolar DCs and alveolar macrophages is suggested by a close anatomic relationship, because the alveolar macrophages are tagged to the alveolar wall close to the fusion line of alveolar septa [52]. Alveolar DCs are not retrievable with bronchoalveolar lavage in normal animals or humans [47]. However, as soon as 4 hours after induction of an inflammatory response with intratracheal Calmette-Guérin bacillus in rats, DCs appear in the lavage [53].

The bronchial and alveolar DCs are not identical in their phenotype. In the rat, alveolar cells are positive for the ED2 marker and are negative for ED1, in contrast to bronchial cells, which are positive for ED1 and negative for ED2 [8]. A similar dichotomy between bronchial and alveolar DCs has been reported in humans [43]. Comparison of function shows that rat bronchial DCs are more efficient at presenting antigens to sensitized T cells, whereas alveolar cells are more potent stimulators for naive T lymphocytes [54]. The former is related to asthma and bronchial hypersensitivity, whereas the latter fact might be involved with acute lung allograft rejection.

Dendritic Cell Function and Modulation by Alveolar Macrophages
Although the methodology employed for retrieval of lung DCs varies from one author to another, results converge to show a dramatic stimulatory activity in a mixed lymphocyte reaction, which is consistently superior to the stimulation observed with macrophages or B lymphocytes [47, 49]. Macrophages are usually weak accessory cells, but their capacities to present antigens are enhanced in pathologic circumstances such as sarcoidosis [55]. The close anatomic relationship between DCs and macrophages noticed on histologic studies suggests a functional interaction. As a matter of fact, presentation of the ovalbumin antigen by autogenic DCs to sensitized T lymphocytes is inhibited in the presence of macrophages [56]. In contrast, depletion of macrophages in a living animal with aerosolized dichloromethylen-diphosphonate allows isolation of DCs with a fivefold increased antigen-presenting activity. Inhibition of the antigen-presenting function is maintained in a co-culture model, where DCs are separated from macrophages with a semipermeable membrane. This observation suggests a humoral modulation by various cytokines, and mainly by tumor necrosis factor {alpha} [52]. Besides macrophages, alveolar pneumocytes may down-regulate the immune response [57].

Dendritic Cells and Lung Diseases
Dendritic cells contained within the normal lung remain different from the cutaneous Langerhans cell. Although they may at times express the CD1a marker, they never contain Birbeck granules. However, histiocytosis X is characterized by large infiltrations with typical Langerhans cells. These cells further express the CD1c marker associated with antigen uptake, which is lacking in the normal cutaneous Langerhans cell [58]. The origin of histiocytosis X is unknown, but it appears that histiocytosis X occurs exclusively in smokers. Several investigators followed the hypothesis that smoking might induce proliferation of Langerhans cells within the lung. Bronchoalveolar lavages were compared in smokers and in nonsmokers. Bronchoalveolar lavage cytology of smokers displayed 1.1% CD1a positive cells, versus 0.1% in nonsmokers; Birbeck granules were found in 0.4% of the cells in smokers and were constantly absent in nonsmokers [59]. Squamous metaplasia induced by tobacco abuse might create an epithelial environment leading to differentiation of precursor cells in the lung or migration originating from the peripheral blood. There also might be a proliferation of exceptional preexisting Langerhans cells. Histologic studies of lung samples collected during lung resections provided similar data. Normal lung contains CD1a-positive cells within the bronchial epithelium and CD1c-positive cells within the alveolar tissue. In smokers, both the absolute number of cells and the number of CD1a cells within the alveolar tissue increase [43]. The humoral mediator of this CD1a differentiation might be GM-CSF, because this cytokine is released by hyperplastic alveolar pneumocytes [60]. Pulmonary infiltrates with DCs have been described in various other chronic lung diseases: idiopathic interstitial fibrosis, bronchiolitis obliterans with organizing pneumonia, desquamative interstitial pneumonia, and allergic alveolitis [61, 62].

The most stimulating point of interest for future research is that DCs have been observed in tumoral and peritumoral tissues. In particular, such infiltrates have been observed together with adenocarcinoma, and more specifically with bronchioloalveolar carcinoma. Correlation of DC infiltrates has been less consistent with other histologies. The trigger seems to be a local production of GM-CSF by pneumocytes or tumoral cells, as ascertained with in situ hybridization studies [60]. The significance of this infiltrate is unclear. Do tumors develop because tumor antigen presentation is deficient, or are these infiltrates on the contrary a sign of an efficient host response? A study by Furukawa and colleagues [63] demonstrated a positive prognostic value for infiltrates with DCs. In a population of 40 patients with stage I adenocarcinoma, 77.5% were found to have infiltrates with DCs; their 5-year survival rate was 86.4%, which was significantly better than the 38.9% observed in patients without DC infiltrates (p < 0.005; {chi}2 = 4.24) [63]. Finally, are tumor-associated DCs the same variety as those observed with histiocytosis? In contrast to histiocytosis Langerhans cells, tumor-associated DCs did not express the MHC class II molecule DP, the Fc{gamma} receptor CD16, the IL-2 receptor CD25, and various adhesion molecules such as CD11b, CD11c, and CD54. Besides, production of IL-1 and interferon {gamma} by tumor-associated DCs was significantly lower. The biologic significance of these differences remains unclear [64].

The major challenge in clinical immunology is the comprehension of the mechanisms that determine chronic rejection. Griffith and colleagues [65] demonstrated in 1989 that chronic irreversible graft dysfunction will develop in 30% to 40% of lung transplant recipients due to bronchiolitis obliterans; this syndrome is at least in part explained by immunologic mechanisms. In an autopsy study of lung transplant recipients who died with bronchiolitis, bronchial mucosa specimens submitted to S-100 protein staining disclosed numerous submucosal infiltrates with DCs. The latter were significantly increased when compared with lung transplant recipients who died without bronchiolitis obliterans, with recipients of an extrathoracic graft, and finally with patients who died free of any respiratory disease [66]. The DC infiltrates seem to originate from the recipient, as has been demonstrated in a rat lung transplant model. Migration of recipient DCs is observed starting at the first postoperative week; at 2 months, DCs have been progressively replaced by recipient-derived DCs. After the second month, these cells form clusters, and finally disappear when histologic modifications of chronic rejection have occurred [67].


   Conclusion
Top
 Footnotes
 Abstract
 Introduction
 Common Characteristics of the...
 Particular Implications Within...
 Conclusion
References
 
To date, our knowledge regarding DCs and their functional pathways is still rudimentary. The ongoing research is impeded by the small absolute number of cells and the difficulties of accurate retrieval. As the potential role of DCs is anticipated to be organ specific, extrapolation from one organ to another is hazardous. However, a major role of DCs in any pathologic change is very likely. Precise identification of the functional mechanisms of DCs may lead to therapeutic use of DC modulation in the hopefully not too remote future.


   Footnotes
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 Footnotes
Abstract
 Introduction
 Common Characteristics of the...
 Particular Implications Within...
 Conclusion
 References
 
Address reprint requests to Dr Massard, Department of Thoracic Surgery, University Hospital of Strasbourg, 67091 Strasbourg, France.


   References
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  1. Knight SC, Stagg AJ. Antigen presenting cell types. Curr Op Immunol 1993;5:374–82.[Medline]
  2. King PD, Katz DR. Mechanisms of dendritic cell function. Immunol Today 1990;11:206–11.[Medline]
  3. Steinman RM. The dendritic cell system and its role in immunogenicity. Annu Rev Immunol 1991;9:271–96.[Medline]
  4. Lafontaine M, Landry D, Montplaisir S. The human thymic dendritic cell phenotype and its modifications in culture. Cell Immunol 1992;142:238–51.[Medline]
  5. Pavli P, Hume DA, Van de Pol E, Doe WF. Dendritic cells, the major antigen-presenting cells of the human colonic lamina propria. Immunology 1993;78:132–41.[Medline]
  6. Zvaifler NJ, Steinman RM, Kaplan G, Lau LL, Rivelis M. Identification of immunostimulatory dendritic cells in the synovial effusions of patients with rheumatoid arthritis. J Clin Invest 1985;76:789–800.
  7. Sertl K, Takemura T, Tschachler E, Ferrans J, Kaliner MA, Shevach EM. Dendritic cells with antigen-presenting capability reside in airway epithelium, lung parenchyma, and visceral pleura. J Exp Med 1986;163:436–51.[Abstract/Free Full Text]
  8. Holt PG, Schon-Hegrad MA, McMenamin PG. Dendritic cells in the respiratory tract. Int Rev Immunol 1990;6:139–49.[Medline]
  9. Inaba K, Inaba M, Deguchi M, et al. Granulocytes, macrophages, and dendritic cells arise from a common major histocompatibility complex class II-negative progenitor in mouse bone marrow. Proc Natl Acad Sci USA 1993;90: 3038–42.[Abstract/Free Full Text]
  10. Reid CDL, Fryer PR, Clifford C, Kirk A, Tikerpae J, Knight SC. Identification of hematopoietic progenitors of macrophages and dendritic Langerhans cells (DL-CFU) in human bone marrow and peripheral blood. Blood 1990;76:1139–49.[Abstract/Free Full Text]
  11. Reid CDL, Stackpole A, Meager A, Tikerpae J. Interactions of tumor necrosis factor with granulocyte-macrophage colony-stimulating factor and other cytokines in the regulation of dendritic cell growth in vitro from early bipotent CD34+ progenitors in human bone marrow. J Immunol 1992;149:2681–8.[Abstract]
  12. Caux C, Dezutter-Dambuyant C, Schmitt D, Banchereau J. GM-CSF and TNF-{alpha} cooperate in the generation of dendritic Langerhans cells. Nature 1992;360:258–61.[Medline]
  13. Bazil V, Strominger JL. Shedding as a mechanism of down-modulation of CD14 on stimulated human monocytes. J Immunol 1991;147:1567–74.[Abstract]
  14. Ruppert J, Schutt C, Ostermeier D, Peters JH. Down-regulation and release of CD14 on human monocytes by IL-4 depends on the presence of serum or GM-CSF. In: Kamperdijk, ed. Dendritic cells in fundamental and clinical immunology. New York: Plenum, 1993:281-6.
  15. Peters HJ, Xu H, Ruppert J, Ostermeier D, Friedrichs D, Gieseler RKH. Signals required for differentiating dendritic cells from human monocytes in vitro. In: Kamperdijk, ed. Dendritic cells in fundamental and clinical immunology. New York: Plenum, 1993:275-80.
  16. De Waal Malefyt R, Figdor CG, Huijbens R, et al. Effects of IL-13 on phenotype, cytokine production, and cytotoxic function of human monocytes. Comparison with IL-4 and modulation by IFN-{gamma} or IL-10. J Immunol 1993;151:6370–81.[Abstract]
  17. Kupiec-Weglinski JW, Austyn JM, Morris PJ. Migration patterns of dendritic cells in the mouse. Traffic from the blood, and T cell-dependent and -independent entry to lymphoid tissues. J Exp Med 1988;167:632–45.[Abstract/Free Full Text]
  18. Larsen CP, Morris PJ, Austyn JM. Migration of dendritic leucocytes from cardiac allografts into host spleens: a novel pathway for initiation of rejection. J Exp Med 1990;171: 307–14.[Abstract/Free Full Text]
  19. Austyn JM, Kupiec-Weglinski JW, Hankins DF, Morris PJ. Migration patterns of dendritic cells in the mouse. Homing to T cell-dependent areas of spleen, and binding within marginal zone. J Exp Med 1988;167:646–51.[Abstract/Free Full Text]
  20. Havenith CEG, van Miert PPMC, Breedijk AJ, Beelen RHJ, Hoefsmit ECM. Migration of dendritic cells into the draining lymph nodes of the lung after intratracheal instillation. Am J Respir Cell Mol Biol 1993;9:484–8.
  21. Van Vugt E, Kamperdijk EWA, Beelen RHJ. Migration patterns of rat peritoneal macrophages and dendritic cells. Transplant Proc 1993;25:2808–10.[Medline]
  22. Young JW, Koulova L, Soergel SA, Clark EA, Steinman RM, Dupont B. The B7/BB1 antigen provides one of several costimulatory signals for the activation of CD4+ T lymphocytes by human blood dendritic cells in vitro. J Clin Invest 1992;90:229–37.
  23. Teunissen MBM, Wormmeester J, Krieg SR, Peters PJ, Vogels IMC, Kapsenberg ML, Bos JD. Human epidermal Langerhans cells undergo profound morphologic and phenotypical changes during in vitro culture. J Invest Dermatol 1990;94:166–73.[Medline]
  24. Thomas R, Davis LS, Lipsky PE. Isolation and characterization of human peripheral blood dendritic cells. J Immunol 1993;150:821–34.[Abstract]
  25. Emile JF, Peuchmaur M, Brousse N. Contrôle des cellules de Langerhans par le GM-CSF. Médecine/Sciences 1994;10:171–5.
  26. Koch F, Heufler C, Kämpgen E, Schneeweiss D, Böck G, Schuler G. Tumor necrosis factor {alpha} maintains the viability of murine epidermal Langerhans cells in culture, but in contrast to granulocyte/macrophage colony-stimulating factor, without inducing their functional maturation. J Exp Med 1990;171:159–71.[Abstract/Free Full Text]
  27. Markowicz S, Engleman EG. Granulocyte-macrophage colony-stimulating factor promotes differentiation and survival of human peripheral blood dendritic cells in vitro. J Clin Invest 1990;85:955–61.
  28. Bowers WE, Ruhoff MS, Goodwell EM. Conditioned medium from activated rat macrophages and the recombinant factors, IL-1ß and GM-CSF, enhance the accessory activity of dendritic cells. Immunobiol 1990;180:362–84.[Medline]
  29. Janeway CA, Bottomly K. Signals and signs for lymphocyte responses. Cell 1994;76:275–85.[Medline]
  30. Shoskes DA, Wood KJ. Indirect presentation of MHC antigens in transplantation. Immunol Today 1994;15:32–8.[Medline]
  31. Van Seventer GA, Shimizu Y, Horgan KJ, Shaw S. The LFA-1 ligand ICAM-1 provides an important costimulatory signal for T cell receptor-mediated activation of resting T cells. J Immunol 1990;144:4579–86.[Abstract]
  32. Springer TA. Adhesion receptors of the immune system. Nature 1990;346:425–34.[Medline]
  33. June CH, Ledbetter JA, Linsley PS, Thompson CB. Role of the CD28 receptor in T-cell activation. Immunol Today 1990;11:211–6.[Medline]
  34. Bjorndahl JM, Sung SSJ, Hansen JA, Fu SM. Human T cell activation: differential response to anti-CD28 as compared to anti-CD3 monoclonal antibodies. Eur J Immunol 1989;19:881–7.[Medline]
  35. Bloemena E, Van Oers RHJ, Weinreich S, Stilma-Meinesz AP, Schellekens PTA, Van Lier RAW. The influence of cyclosporin A on the alternative pathways of human T cell activation in vitro. Eur J Immunol 1989;19:943–6.[Medline]
  36. Kim HS, Zhang X, Choi YS. Activation and proliferation of follicular dendritic cell-like cells by activated T lymphocytes. J Immunol 1994;153:2951–61.[Abstract]
  37. Halloran PF, Broski AP, Batiuk TD, Madrenas J. The molecular immunology of acute rejection: an overview. Transplant Immunol 1993;1:3–27.[Medline]
  38. Dayer JM, Isler P, Nicod LP. Adhesion molecules and cytokine production. Am Rev Respir Dis 1993;148:S70–4.[Medline]
  39. Nicod LP, El Habre F. Adhesion molecules on human lung dendritic cells and their role for T-cell activation. Am J Respir Cell Mol Biol 1992;7:207–13.
  40. Quin L, Chavin KD, Lin J, Yagita H, Bromberg JS. Anti-CD2 receptor and anti-CD2 ligand (CD48) antibodies synergize to prolong allograft survival. J Exp Med 1994;179:341–6.[Abstract/Free Full Text]
  41. Rowden G, Sheikh K, Misra B, Higley H, Relfson M, Connelly E. Investigations of glial proteins S-100 and FGA in human dendritic cells in the epidermis and lymph nodes. J Invest Dermatol 1982;78:354–5.
  42. Betjes MGH, Haks MC, Tuk CW, Beelen HJ. Monoclonal antibody EBM11(anti-CD68) discriminates between dendritic cells and macrophages after short-term culture. Immunobiol 1991;183:79–87.[Medline]
  43. Soler P, Moreau A, Basset F, Hance AJ. Cigarette smoking-induced changes in the number and differentiated state of pulmonary dendritic cells/Langerhans cells. Am Rev Respir Dis 1989;139:1112–7.[Medline]
  44. Schon-Hegrad M, Oliver J, McMenamin PG, Holt PG. Studies on the density, distribution, and surface phenotype of intraepithelial class II major histocompatibility complex antigen (Ia)-bearing dendritic cells in the conducting airways. J Exp Med 1991;173:1345–56.[Abstract/Free Full Text]
  45. Holt PG, Degebrodt A, Venaille T, et al. Preparation of interstitial lung cells by enzymatic digestion of tissue slices: preliminary characterization by morphology and performance in functional assays. Immunology 1985;54:139–47.[Medline]
  46. Holt PG, Robinson BWS, Reid M, et al. Extraction of immune and inflammatory cells from human lung parenchyma: evaluation of an enzymatic digestion procedure. Clin Exp Immunol 1986;66:188–200.[Medline]
  47. Nicod LP, Lipscomb MF, Weissler JC, Lyons CR, Albertson J, Toews GB. Mononuclear cells in human lung parenchyma. Characterization of a potent accessory cell not obtained by bronchoalveolar lavage. Am Rev Respir Dis 1987;136:818–23.[Medline]
  48. Nicod LP, Lipscomb MF, Toews GB, Weissler JC. Separation of potent and poorly functional human lung accessory cells based on autofluorescence. J Leukocyt Biol 1989;45:458–65.[Abstract]
  49. Nicod LP, Lipscomb MF, Weissler JC, Toews GB. Mononuclear cells from human lung parenchyma support antigen-induced T lymphocyte proliferation. J Leukocyt Biol 1989;45:336–44.[Abstract]
  50. Nelson DJ, McMenamin C, McWilliam AS, Brenan M, Holt PG. Development of the airway intraepithelial dendritic cell network in the rat from class II major histocompatibility (Ia)-negative precursors: differential regulation of Ia expression at different levels of the respiratory tract. J Exp Med 1994;179:203–12.[Abstract/Free Full Text]
  51. Holt PG, Oliver J, McMenamin C, Schon-Hegard MA. Studies on the surface phenotype and functions of dendritic cells in parenchymal lung tissue of the rat. Immunology 1992;75:582–7.[Medline]
  52. Holt PG, Oliver J, Bilyk N, McMenamin C, McMenamin PG, Kraal G, Thepen T. Downregulation of the antigen presenting cell function(s) of pulmonary dendritic cells in vivo by resident alveolar macrophages. J Exp Med 1993;177:397–407.[Abstract/Free Full Text]
  53. Havenith CEG, Breedijk AJ, Hoefsmit ECM. Effect of bacillus Calmette-Guérin inoculation on numbers of dendritic cells in bronchoalveolar lavages of rats. Immunobiol 1992;184:336–47.[Medline]
  54. Gong JL, McCarthy KM, Telford J, Tamatani T, Miyasaka M, Schneeberger EE. Intraepithelial airway dendritic cells: a distinct subset of pulmonary dendritic cells obtained by microdissection. J Exp Med 1992;175:797–807.[Abstract/Free Full Text]
  55. Gant VA, Shakoor Z, Barbosa IL, Hamblin AS. Normal and sarcoid alveolar macrophages differ in their ability to present antigen and to cluster with autologous lymphocytes. Clin Exp Immunol 1991;86:494–9.[Medline]
  56. Holt PG, Schon-Hegrad MA, Oliver J. MHC class II antigen-bearing dendritic cells in pulmonary tissues of the rat. Regulation of endogenous antigen presentation activity by endogenous macrophage populations. J Exp Med 1988;167:262–74.[Abstract/Free Full Text]
  57. Paine R, Mody CH, Chavis A, Spahr MA, Turka LA, Toews GB. Alveolar epithelial cells block lymphocyte proliferation in vitro without inhibiting activation. Am J Respir Cell Mol Biol 1991;5:221–5.
  58. Tazi A, Bonay M, Grandsaigne M, Battesti JP, Hance AJ, Soler P. Surface phenotype of Langerhans cells and lymphocytes in granulomatous lesions from patients with pulmonary histiocytosis X. Am Rev Respir Dis 1993;147:1531–6.[Medline]
  59. Casolaro A, Bernaudin JF, Saltini C, Ferans VJ, Crystal RG. Accumulation of Langerhans cells on the epithelial surface of the lower respiratory tract in normal subjects in association with cigarette smoking. Am Rev Respir Dis 1988;137:406–11.[Medline]
  60. Tazi A, Bouchonnet F, Grandsaigne M, Boumsell L, Hance AJ, Soler P. Evidence that granulocyte macrophage-colony-stimulating factor regulates the distribution and differentiated state of dendritic cells/Langerhans cells in human lung and lung cancers. J Clin Invest 1993;91:566–76.
  61. Wood GS, Turner RR, Shiurba RA, Eng L, Warnke RA. Human dendritic cells and macrophages. In situ immunophenotypic definition of subsets that exhibit specific morphologic and microenvironmental characteristics. Am J Pathol 1985;119:73–82.[Abstract]
  62. Hammar S, Bockus D, Remington F, Bartha M. The widespread distribution of Langerhans cells in pathologic tissues. Hum Pathol 1986;17:894–905.[Medline]
  63. Furukawa T, Watanabe S, Kodama T, Sato Y, Shimosato Y, Suemasu K. T-zone histiocytes in adenocarcinoma of the lung in relation to post-operative prognosis. Cancer 1985;56:2651–6.[Medline]
  64. Colasante A, Poletti V, Rosini S, Ferracini R, Musiani P. Langerhans cells in Langerhans cell histiocytosis and peripheral adenocarcinomas of the lung. Am Rev Respir Dis 1993;148:752–9.[Medline]
  65. Griffith BP, Paradis IL, Zeevi A, et al. Immunologically mediated disease of the airways after pulmonary transplantation. Ann Surg 1988;208:371–8.[Medline]
  66. Yousem SA, Ray L, Paradis IL, Dauber JA, Griffith BP. Potential role of dendritic cells in bronchiolitis obliterans in heart-lung transplantation. Ann Thorac Surg 1990;49:424–8.[Abstract]
  67. Uyama T, Winter JB, Sakiyama S, Monden Y, Groen G, Prop J. Replacement of dendritic cells in the airways of rat lung allografts. Am Rev Respir Dis 1993;148:760–7.[Medline]



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