Inhibition of alloreactivity by mAb MR6: differential effects on IL-2- and IL-4-producing human T cells
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mAb MR6 has previously been shown to block both IL-4-induced T cell proliferation and IL-4-dependent IgE production, suggesting a functional association between the antigen detected by MR6 (gp200-MR6) and the human IL-4 receptor. In this study the potential modulatory effects of mAb MR6 on IL-4 function have been further analysed in alloantigen-specific assays for cytotoxic and Th cell maturation, mature cytotoxic T cell killing, helper cell proliferation, and generation of IL-2- and IL-4-producing Th cells in a mixed lymphocyte reaction (MLR). Our data show that mAb MR6 has an inhibitory effect on both clonal expansion and maturation of cytotoxic T lymphocyte precursors within the alloreactive T cell population. mAb MR6 had no effect on the maturation of Th lymphocyte precursors (assayed by IL-2 production). However, this mAb had striking differential effects on cytokine production in MLR cultures, showing total ablation of IL-4 but no alteration of IL-2 levels in the supernatant medium. The absence of IL-4 from culture supernatants could be due to the fact that mAb MR6 is blocking cytokine production, that it is speeding up IL-4 internalization and utilization or that it inhibits the expansion of the T cell subset(s) that secretes IL-4. The data demonstrate that the action of mAb MR6 is focused on the IL-4-producing population and raise the possibility that gp200-MR6 may play an important role in this aspect of IL-4 function.