Dai Jihong, Megjugorac Nicholas J, Gallagher Grant E, Yu Raymond Y L, Gallagher Grant
Genetic Immunology Laboratory, HUMIGEN, The Institute for Genetic Immunology, Hamilton, NJ 08690, USA.
Blood. 2009 Jun 4;113(23):5829-38. doi: 10.1182/blood-2008-09-179507. Epub 2009 Apr 3.
IFN-lambda1 (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-lambda1-specific receptor, IL-28Ralpha, and are responsive to IFN-lambda1. Expression of Th2 cytokines (IL-4 and IL-13) was suppressed in naive and memory CD4(+) T cells by IFN-lambda1, without affecting their proliferation. Further, acquisition of IL-4Ralpha expression after stimulation was inhibited by IFN-lambda1, as was GATA3 expression. Finally, IFN-lambda1 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-lambda1 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.
干扰素-λ1（IL-29）在抑制人类Th2反应中发挥着新出现的作用。在此，我们证明，初始和记忆性人类CD4(+) T细胞均表达干扰素-λ1特异性受体IL-28Rα的mRNA，并且对干扰素-λ1有反应。干扰素-λ1抑制了初始和记忆性CD4(+) T细胞中Th2细胞因子（IL-4和IL-13）的表达，而不影响它们的增殖。此外，干扰素-λ1抑制了刺激后IL-4Rα表达的获得，GATA3表达也受到抑制。最后，干扰素-λ1减少了“中央记忆”T细胞分化为“效应记忆”T细胞时伴随的细胞表面表型变化。综上所述，我们的数据描述了干扰素-λ1独特的免疫调节作用，并确定了在循环中的初始和记忆性CD4(+) T细胞中减少现有Th2反应和调节新反应的新机制。
