TY - JOUR
T1 - Evidence that anti-CD8 abrogates anti-CD4-mediated clonal anergy but allows allograft survival in mice1
AU - Song, Howard K.
AU - Alters, Susan E.
AU - Fathman, C. Garrison
PY - 1993/1
Y1 - 1993/1
N2 - 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-Thyl.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 allo-reactive T cells to anti-T-cell receptor-specific cross-linking. Interestingly, the potentially alloreactive T cell subsets of recipient mice ÇV05+ and V/?l 1+) 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-Thyl.2 treated recipient mice, which rejected islet allografts despite similar levels of initial T cell depletion, suggest that unresponsiveness to alloan-tigen 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.
AB - 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-Thyl.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 allo-reactive T cells to anti-T-cell receptor-specific cross-linking. Interestingly, the potentially alloreactive T cell subsets of recipient mice ÇV05+ and V/?l 1+) 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-Thyl.2 treated recipient mice, which rejected islet allografts despite similar levels of initial T cell depletion, suggest that unresponsiveness to alloan-tigen 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.
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U2 - 10.1097/00007890-199301000-00025
DO - 10.1097/00007890-199301000-00025
M3 - Article
C2 - 8420037
AN - SCOPUS:0027389792
SN - 0041-1337
VL - 55
SP - 133
EP - 139
JO - Transplantation
JF - Transplantation
IS - 1
ER -