Stat6 regulation of in vivo IL-4 responses

Although in vitro development of a Th2 response from naive CD4(+) T cells i s Stat6 dependent, mice immunized with a goat Ab to mouse IgD have been rep orted to produce a normal primary IL-4 response in Stat6-deficient mice. Ex periments have now been performed with mice immunized with more conventiona l Ags or inoculated with nematode parasites to account for this apparent di screpancy. The ability of an immunogen to induce a primary in vivo IL-4 res ponse in Stat6-deficient mice was found to vary directly with its ability t o induce a strong type 2 cytokine-biased response in normal mice, Even immu nogens, however, that induce strong primary IL-4 responses in Stat6-deficie nt mice induce poor memory IL-4 responses in these mice. Consistent with th is, Stat6-deficient CD4(+) T cells make relatively normal IL-4 responses wh en stimulated in vitro for 3 days with anti-CD3 and anti-CD28, but poor IL- 4 responses if they are later restimulated with anti-CD3. Thus, Stat6 signa ling enhances primary IL-4 responses that are made as part of a type 0 cyto kine response (mixed type 1 and type 2) and is required for normal developm ent or survival of Th2 memory cells.