Subsets of activated CD4 T lymphocytes refractory for secretion of IL-2 are distinguished by expression of Ly-6A/E in BALB/c mice.

Ly-6A/E, a cell surface glycosylphosphatidylinositol-anchored protein that modulates T cell activation, is expressed on developing and mature T cells and is tightly regulated in a haplotype- and subset-specific manner. We examined whether Ly-6A/E(low)CD4+ and Ly-6A/E(high)CD4+ T cells comprised functional subsets. Peripheral CD4+ T cells were primed in vitro with Con A in the presence or absence of IL-4 or IFN-gamma, sorted for Ly-6A/E expression, and restimulated to induce lymphokine production. Regardless of priming conditions, IL-2 production by Ly-6A/E(high)CD4+ effector T cells was markedly reduced (mean = 83%) compared to the Ly-6A/E(low)CD4+ subset. The Ly-6A/E(high)CD4+ subset also produced less IFN-gamma than Ly-6A/E(low)CD4+ cells and little IL-4 when primed without exogenous IL-4. In contrast, Ly-6A/E(high)CD4+ cells primed with exogenous IL-4 produced ample IL-4 and IFN-gamma. Interestingly, the difference in IL-2 production between Ly-6A/E(low) and Ly-6A/E(high)CD4+ subsets was not due to a failure of the Ly-6A/E(low)CD4+ cells to become primed because substantially greater amounts of IL-2 and IL-4 were produced by the Con A-pretreated Ly-6A/E(low)CD4+ subset in comparison to unprimed Ly-6A/E(low)CD4+ cells. Taken together these data suggest Ly-6A/E marks a subset of CD4+ effector T cells that differs from Ly-6A/E(low)CD4+ cells by a greatly reduced capacity to produce IL-2 but not IL-4.