Evidence that anti-CD8 abrogates anti-CD4-mediated clonal anergy but allows allograft survival in mice.
Monoclonal antibodies directed against different T cell subpopulations have been used in several rodent models of transplantation to induce long-term unresponsiveness to allografts by a variety of mechanisms. To investigate whether different mechanisms may be operative when different regimens of mAb therapy are used, we studied the effects of various combinations of anti-T-cell antibody treatment on the induction of tolerance in a mouse islet allograft model. Anti-CD4 mAb alone, anti-CD8 mAb alone, anti-CD4 mAb plus anti-CD8 mAb, and anti-Thy1.2 mAb alone were given at the time of engraftment. Only the anti-CD4 mAb and the anti-CD4 mAb plus anti-CD8 mAb regimens were successful in inducing permanent unresponsiveness to islet allografts. We have previously shown that anti-CD4 mAb alone induces permanent unresponsiveness to islet allografts by a mechanism of clonal anergy, as demonstrated by unresponsiveness of potentially alloreactive T cells to anti-T-cell receptor-specific cross-linking. Interestingly, the potentially alloreactive T cell subsets of recipient mice (V beta 5+ and V beta 11+) made unresponsive to islet allografts by anti-CD4 mAb plus anti-CD8 mAb therapy were not found to be anergic using the same assay. Differences between the repopulation kinetics of CD8+ T cells of anti-CD4 mAb plus anti-CD8 mAb treated recipient mice, which accepted islet allografts, and anti-Thy1.2 treated recipient mice, which rejected islet allografts despite similar levels of initial T cell depletion, suggest that unresponsiveness to alloantigen may have been induced in anti-CD4 mAb plus anti-CD8 mAb treated recipients by clearance of donor passenger leukocytes during prolonged CD8+ T cell depletion.
Song
H K
HK
Department of Medicine, Stanford University School of Medicine, California 94305-5111.
Alters
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SE
Fathman
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CG
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology*; D016525:Antigenic Modulation / Q000276:immunology; D000961:Antilymphocyte Serum / Q000276:immunology*; D015704:CD4 Antigens / Q000276:immunology*; D016827:CD8 Antigens / Q000276:immunology*; D006084:Graft Rejection / Q000276:immunology*; D006085:Graft Survival / Q000276:immunology*; D007108:Immune Tolerance / Q000276:immunology*; D016381:Islets of Langerhans Transplantation / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D014184:Transplantation, Homologous
D000911:Antibodies, Monoclonal; D000961:Antilymphocyte Serum; D015704:CD4 Antigens; D016827:CD8 Antigens