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An mAb MRC OX-22, reactive with the high molecular weight forms of the rat leukocyte-common antigen, has revealed a heterogeneity among CD4+ T cells in this species. Approximately two-thirds are CD4+, OX-22+, and one-third are CD4+, OX-22-. This phenotypic heterogeneity was found to be associated with a functional one. CD4+, OX-22+ cells proliferated well in mixed leukocyte culture, responded to the T cell mitogen Con A, and produced IL-2 on activation. In contrast, the CD4+, OX-22- cells performed poorly in these assays, but unlike CD4+, OX-22+ cells, did provide effective help for B cells. By sampling supernatants from cultures containing primed B cells and either of the two CD4+ T cell subsets, it was shown that, when specific antigen was included in the cultures, those containing the OX-22- subset of CD4+ cells produced high levels of antibody and some IL-2, whereas those containing the OX-22+ cells produced neither. In contrast, when specific antigen was replaced by Con A, the B cell cultures supplemented with CD4+, OX-22+ cells synthesized much higher levels of IL-2 than those containing CD4+, OX-22- cells, but only the latter cultures produced detectable levels of antibody. The data show that inducer/helper T cells comprise two functional subsets: one that, on appropriate stimulation, synthesizes high levels of IL-2, and may therefore be presumed to play an important role in cell-mediated immunity, and another that plays an essential role in humoral responses to soluble antigens. The significance of this functional heterogeneity, with regard to the possible independent regulation of cellular and humoral responses, is briefly considered.

T cells that help B cell responses to soluble antigen are distinguishable from those producing interleukin 2 on mitogenic or allogeneic stimulation.