Self-tolerance and H-2 antigen expression in semi-allogeneic radiation chimeras are controlled by the extrathymic host environment.

Experiments with thymus-grafted radiation chimeras have implicated the H-2 type of the radio-resistant portion of the thymus as determining self for H-2 restricted T-cell responses. (P1 X P2)F1----P1 chimeras, shown to be fully reconstituted with donor haemopoietic cells, have displayed intolerance to P2 H-2 antigens and expressed aberrant levels of P2 H-2 on their spleen cells. We used semi-allogeneic radiation chimeras grafted with fetal thymuses from parental strain donors to compare the relative contributions of the thymus and the extrathymic periphery in determining self-tolerance and in modulating the H-2 phenotype of heterozygous chimeric spleen cells. As analysed by the rosetting titres of anti-H-2 antisera on chimeric spleen cells, by parental skin graft rejection, and by spleen cell anti-parent cytotoxicity after culture with parental stimulators, the decreased expression of non-host parental H-2 antigens was associated with anti-P2 T-cell reactivity, regardless of the H-2 type of the thymus. The donor thymus did not affect tolerance to parental H-2 or cause aberrant expression of H-2 antigens on spleen cells of syngeneic F1----F1 thymus-grafted chimeras.