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 Blood, 4 June 2009, Vol. 113, No. 23, pp. 5829-5838.
Prepublished online as a Blood First Edition Paper on April 3, 2009; DOI 10.1182/blood-2008-09-179507.

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IMMUNOBIOLOGY

IFN-{lambda}1 (IL-29) inhibits GATA3 expression and suppresses Th2 responses in human naive and memory T cells

Jihong Dai1, Nicholas J. Megjugorac1, Grant E. Gallagher1, Raymond Y. L. Yu1, and Grant Gallagher1

1 Genetic Immunology Laboratory, HUMIGEN, The Institute for Genetic Immunology, Hamilton, NJ

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.


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