Inhibition of alloreactivity by mAb MR6: differential effects on IL-2- and IL-4-producing human T cells

mAb MR6 has previously been shown to block both IL-4-lnducedT cell proliferation and IL-4-dependent IgE production, suggestinga functional association between the antigen detected by MR6(gp200-MR6) and the human IL-4 receptor. In this study the potentialmodulatory effects of mAb MR6 on IL-4 function have been furtheranalysed in alloantigen-specific assays for cytotoxlc and T_hcell maturation, mature cytotoxlc T cell killing, helper cellproliferation, and generation of IL-2- and IL-4-produclng T_hcells in a mixed lymphocyte reaction (MLR). Our data show thatmAb MR6 has an inhibitory effect on both clonal expansion andmaturation of cytotoxlc T lymphocyte precursors within the alloreactlveT cell population. mAb MR6 had no effect on the maturation ofT_h lymphocyte precursors (assayed by IL-2 production). However,this mAb had striking differential effects on cytoklne productionin MLR cultures, showing total ablation of IL-4 but no alterationof IL-2 levels in the supernatant medium. The absence of IL-4from culture supernatants could be due to the fact that mAbMR6 is blocking cytoMne production, that it is speeding up IL-4internalization and utilization or that it inhibits the expansionof the T cell subset(s) that secretes IL-4. The data demonstratethat the action of mAb MR6 is focused on the IL-4-producingpopulation and raise the possibility that gp200-MR6 may playan important role in this aspect of IL-4 function.