C. Garrison Fathman

Publication Details

  • EVIDENCE THAT ANTI-CD8 ABROGATES ANTI-CD4 MEDIATED CLONAL ANERGY BUT ALLOWS ALLOGRAFT SURVIVAL IN MICE TRANSPLANTATION Song, H. K., Alters, S. E., Fathman, C. G. 1993; 55 (1): 133-139

    Abstract:

    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.

    View details for Web of Science ID A1993KH66000025

    View details for PubMedID 8420037

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