Immunological consequences of T cell-specific expression of H-2Kb molecules in transgenic mice.

CBA (H-2k) mice carrying a H-2Kb transgene (CD2Kb) linked to transcriptional control elements from the human CD2 gene express H-2Kb at high levels on all thymocytes and peripheral T cells. However, skin grafts from two independent transgenic lineages, CD2Kb-2 and CD2Kb-3, are not rejected by recipient CBA mice. Although mice from both lineages tolerate H-2Kb disparate skin grafts, tolerance is maintained by different mechanisms because H-2Kb-specific cytotoxic T cells cannot be generated in vitro using CD2Kb-2 responder spleen cells, but can be generated when responder cells are from CD2Kb-3 mice. Furthermore, H-2Kb-restricted cytotoxic T cell responses directed against minor histocompatibility antigens can be obtained from CD2Kb-2 responder mice. Thus, negative and positive selection of immature thymocytes seems to take place in CD2Kb-2 mice, even though the pattern of H-2Kb expression is modified by the CD2Kb transgene. In contrast, H-2Kb-specific cytotoxic T cell precursors are not eliminated in CD2Kb-3 mice, even though all thymocytes express H-2Kb in these mice. However, these potentially autoreactive H-2Kb-specific T cells are apparently inactive in vivo and fail to lyse syngeneic CD2Kb-3 target cells in vitro, even when activated to lyse other H-2Kb-expressing cells. These results reveal that tolerance in CD2Kb-3 mice is induced either by a non-deletional mechanism or by partial elimination of a subset of cytotoxic T cell precursors capable of recognizing H-2Kb as a target antigen.