Ann Thorac Surg 1998;66:2026
© 1998 The Society of Thoracic Surgeons
Invited Commentary
Patrick G. Hogan, FRCPAa,
Mark F. O’Brien, FRACSb
a Lions Human Immunology Laboratories, The University of Queensland, Princess Alexandra Hospital, Brisbane 4102, Australia
b The Prince Charles Hospital, Rode Road, Chermside, Brisbane 4032, Australia
Invited commentary
This report by Hoekstra and colleagues is one of several contributions from this group to the ongoing debate about how the immune system detects cryopreserved valve allografts (VAs) and how much damage can be done to the VA as a result. They and others have uncovered vigorous anti–donor immunoglobulin G and T-cell–mediated responses both in the peripheral blood and explanted VA from recipients. Initiation of this allogeneic response requires intimate and specific contact between recipient T cells and viable donor cells expressing human leukocyte antigen (HLA) class II antigens. Only "professional antigen-presenting cells," which display unique activation receptors and high-density membrane HLA class II, are capable of unleashing the cascade of T-cell activation in response to mismatched HLA antigens. In the cryopreserved VA, no cell has so far been identified for this pivotal role. Hoekstra and associates and others have previously shown that valve leaflet endothelial cells can activate T cells; but there is a consensus that insufficient numbers of endothelial cells survive cryopreservation to mediate this function. Similarly, valve fibroblasts and myocytes lack both the critical numbers and antigen-presenting capacity. Hoekstra and coworkers correctly propose the vascular dendritic cell as the most likely initiator, as relatively few of these extremely potent cells would be needed to trigger the anti–VA response.
After activation, can T cells and immunoglobulin G damage the VA and reduce its functional life span? Opinion remains divided. The lack of lymphocytic infiltration in VA explants suggests that mechanical forces may be the main cause of dysfunction. However, proponents for immunologic failure argue that few explants are actually removed and appropriately examined during the likely period of immunologic injury. Our results and those of Hoekstra and colleagues suggest that VA injury may happen between 1 and 4 months after implantation, based on the time course of T-cell reactivity and antibody levels. Weak and indirect evidence for immunologic injury also comes from retrospective studies attempting to link VA function and longevity to the degree of HLA mismatch and the presence of performed donor-reactive antibody in donor–recipient pairs.
Decisions to implement HLA matching and antibody screening or immune suppression must wait until more is known about mechanisms of VA damage. Every opportunity should be taken to examine explanted VAs and normal valves with immunochemical methods to detect dendritic cells and lymphocyte surface markers. The effect of cryopreservation and conditioning treatments on valve dendritic cells would also be of great interest. These strategies, together with ongoing studies of animal VA models and HLA matching by several groups, should indicate clearly whether current practice can be improved.
Related Article
-
Immunogenic human leukocyte antigen class II antigens on human cardiac valves induce specific alloantibodies
- Franciska M.E. Hoekstra, Marian Witvliet, Christiaan Y. Knoop, Claes Wassenaar, Ad J.J.C. Bogers, Willem Weimar, and Frans H.J. Claas
Ann. Thorac. Surg. 1998 66: 2022-2026.
[Abstract]
[Full Text]
[PDF]
