The lymphoid cell populations required for induction of tolerance of different subsets of alloantigen-reactive T cells.

Previous studies have demonstrated that i.v. presensitization of C57BL/6 (B6) mice with class I H-2-disparate B6-C-H-2bml (bml) spleen cells induced potent suppression of anti-bml CD8+ T cell-mediated responses in vitro as well as suppression of the allograft response. The present study analyzes the population of donor bml cells required for suppression of the generation of the cellular subsets involved in the in vitro and in vivo immune responses. Anti-bml CD8+ helper T cell (proliferative/IL-2-producing) activities were almost completely eliminated by i.v. inoculation of bml whole blood or various (T or B cell) fractions of spleen cells. However, anti-bml CD8+ cytotoxic T lymphocyte capacity was significantly reduced by i.v. sensitization with bml T cell-containing, but not with T cell-depleted splenic fractions. In B6 mice receiving bml skin grafts following i.v. sensitization with T-depleted bml spleen cells, marginal Th activity was induced. However, the CTL response was equal to that observed in unsensitized mice, and allograft survival was not prolonged. Prolongation of bml graft survival was achieved by i.v. presensitization with bml T cell fraction, indicating that bml T cells were a requirement for suppression of graft rejection in the B6-bml combination. In contrast, in the B6-C-H-2bml2 (bml2) combination in which CD4+ T cells are responding to bml2 alloantigens, only the B cell fraction was capable of prolonging bm12 graft survival. These results indicate that functionally and phenotypically different subsets of alloantigen-reactive T cells are rendered unresponsive by i.v. presensitization with distinct fractions of donor lymphoid cells.