Highly purified populations of C57BL/6 (B6) L3T4+ and Lyt-2+ T cell subsets were compared for their capacity to exert alloreactivity to class I vs. class II H-2 differences in vivo. B6 Lyt-2+ cells responded strongly to the class I different mutant, bm1, as manifested by DNA synthesis in the spleen of irradiated mice followed by entry of blast cells into thoracic duct lymph, induction of splenomegaly in newborn mice, production of lethal GVHD in irradiated mice, and skin allograft rejection. By all of these parameters, B6 Lyt-2+ cells showed almost total unresponsiveness to the class II-different mutant, bm12. Reciprocal results were observed with B6 L3T4+ cells, these cells responding strongly against bm12 but not against bm1. In the case of purified T cell subsets from other strains, CBA/Ca and B10.BR L3T4+ cells both responded well to a full H-2 difference. Responses by Lyt-2+ cells from these strains were weaker, especially for CBA/Ca cells. The implications of these findings are discussed.

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