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Right arrow Lung - transplantation

Ann Thorac Surg 2003;75:1123-1127
© 2003 The Society of Thoracic Surgeons

Original article: general thoracic

CTLA4Ig-gene transfection inhibits obliterative airway disease in rats

Yusuke Kita, MDa*, Kazuya Suzuki, MDb, Hiroshi Nogimura, MDa, Tsuyoshi Takahashi, MDb, Teruhisa Kazui, MDb

a Department of Thoracic Surgery, Haibara General Hospital, Shizuoka, Japan
b First Department of Surgery, Hamamatsu University School of Medicine, Hamamatsu, Japan

Accepted for publication October 25, 2002.

* Address reprint requests to Dr Kita, Department of Thoracic Surgery, Haibara General Hospital, 2887-1 Hosoe, Haibara-cho, Haibara-gun, Shizuoka-pref, Japan 421-0493
e-mail: kita21{at}aqua.ocn.ne.jp

BACKGROUND: Obliterative airway disease (OAD) is a major cause of long-term morbidity following lung transplantation. Its pathologic characteristics are small-airway inflammation and occlusion by fibrous tissue. However, the pathogenesis is uncertain and therapy is ineffective. This study presents the effects of CTLA4Ig-gene therapy on OAD in heterotopically transplanted rat tracheal allografts.

METHODS: Dark Agouti (DA, RT1a) allografts and Lewis (LEW, RT1l) isografts were transplanted into Lewis recipients. The tracheal graft was transplanted heterotopically into the subcutaneous pocket into the back. Adenoviral vectors (1.0x109 pfu) containing the CTLA4Ig-gene (AdCTLA4Ig) or the LacZ-gene (AdLacZ) were injected into the tail vein immediately after grafting. Grafts were harvested and examined after more than 35 days for mononuclear cell infiltration development and lumen occlusion with fibrosis.

RESULTS: Fully allogenic DA tracheas, treated with AdCTLA4Ig had significantly lower pathologic scores and infiltrating scores than the control allografts. The pathologic findings of the grafts, treated with AdCTLA4Ig, were very similar to those of the syngeneic grafts. The animals experienced no adverse events during follow-up. No evidence of vector-mediated tissue damage was seen in any graft.

CONCLUSIONS: Adenoviral vectors containing the CTLA4Ig-gene markedly inhibited the obliteration of the airway lumen. OAD may be associated with T-cell responses against graft tissue and alloimmune injury.






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