Minor but not major histocompatibility antigens of thymus epithelium tolerize precursors of cytolytic T cells.

Treatment of fetal thymuses with 2-deoxyguanosine depletes these organs of many haematopoietic cells, and if such thymuses are transplanted into allogeneic athymic nude mice, intrathymic development of cytolytic T-lymphocyte precursors (CTL-P) occurs, including those which are specific for class I major histocompatibility complex (MHC) antigens expressed by the thymus epithelium. Thus, T cells from BALB/c (H-2d) nude mice transplanted with allogeneic C57BL/6 (H-2b) thymic epithelium can be stimulated in vitro to produce CTL specific for H-2b class I MHC antigens. We report here that thymocytes and lymph node T cells from such mice are responsive in mixed leukocyte reaction in the absence of exogenous growth factors, indicating that lack of tolerance is manifest at the level of CTL-P and proliferating T cells. We also show that T cells from such mice are tolerant to minor histocompatibility antigens of the thymus donor in the context of MHC antigens of the recipient. The results indicate that haematopoietic rather than epithelial cells tolerize CTL-P and that donor-type minor but not major histocompatability antigens can be presented in tolerogenic form by haematopoietic cells expressing recipient-type MHC antigens.