Tolerance of thymic cytotoxic T lymphocytes to allogeneic H-2 determinants encountered prethymically: evidence for expression of anti-H-2 receptors prior to entry into the thymus.

This study has assessed the possibility that anti-H-2 receptors are expressed on T-cell precursors prior to their entry into the thymus. Parental strain A thymus was transplanted into either normal or thymectomized (A x B)F1 mice which were then irradiated and reconstituted with strain A bone marrow. The cells repopulating the engrafted strain A thymus were shown to be of donor bone marrow origin. Thus, strain A thymocytes were differentiating within a syngeneic thymus, after exposure to allogeneic strain B major histocompatibility complex (MHC) determinants of the irradiated F1 host. The cells repopulating the engrafted thymus were assessed for their ability to generate alloreactive cytotoxic T lymphocyte responses and were found to be specifically tolerant to allogeneic strain B MHC determinants. This tolerance existed in the absence of detectable suppression and in the absence of detectable strain B MHC determinants intrathymically. These data are most consistent with the concept that precursor T cells express anti-MHC receptors prior to their entry into the thymus and that exposure to MHC determinants prethymically results in their functional inactivation.