IFN-λ1 (IL-29) inhibits GATA3 expression and suppresses Th2 responses in human naive and memory T cells

IFN-lambda 1 (IL-29) plays a novel, emerging role in the inhibition of human Th2 responses. Here, we demonstrate that both naive and memory human CD4(+) T cells express mRNA for the IFN-lambda 1-specific receptor, IL-28R alpha, and are responsive to IFN-lambda 1. Expression of Th2 cytokines (IL-4 and IL-13) was suppressed in naive and memory CD4(+) T cells by IFN-lambda 1, without affecting their proliferation. Further, acquisition of IL-4R alpha expression after stimulation was inhibited by IFN-lambda 1, as was GATA3 expression. Finally, IFN-lambda 1 diminished the change in cell-surface phenotype that accompanies differentiation of "central memory" T cells into "effector memory" T cells. Taken together, our data describe unique immunomodulatory effects of IFN-lambda 1 and identify novel mechanisms for the reduction of existing Th2 responses and the regulation of new ones, in circulating naive and memory CD4(+) T cells. (Blood. 2009; 113: 5829-5838)