Type I IFN induces antiviral and antiproliferative effects in cells through the formation of Stat1/Stat2 heterodimers or Stat1 homodimers. Stat2-deficient primary mouse embryonic fibroblasts (PMEFs) responded poorly to IFN-a but normally to IFN-y, whereas Stat2-deficient macrophages responded normally to IFN-a and IFN-y, suggesting that IFN-a-induced gene upregulation in macrophages is Stat2-independent (16). Stat2-deficient PMEFs were more sensitive to VSV in the presence or absence of IFN-a and IFN-y. In these cells, the failure of an autocrine loop of induction of IFN-a by IFN-y is believed to be responsible for the failure of IFN-y to afford protection to the cells. Consistently, Stat2-null animals were more susceptible to VSV at doses up to 6 logs lower than for controls. Antagonism of T-cell proliferation by IFN-a after in vivo challenge with dexamethasone was absent in Stat2-deficient animals, resulting in enhanced recovery of thymic T-cell populations.

0 0

Post a comment