AN INTERLEUKIN-4 (IL-4)-INDEPENDENT PATHWAY FOR CD4(-CELL IL-4 PRODUCTION IS REVEALED IN IL-4 RECEPTOR-DEFICIENT MICE() T)

IL-4 receptor alpha chain (IL-4R alpha)-deficient mice were generated by gene-targeting in BALB/c embryonic stem cells, Mutant mice showed a loss of IL-4 signal transduction and functional activity. The lack of IL-4R alpha resulted in markedly diminished, but not absent, TH2 resp onses after infection with the helminthic parasite Nippostrongylus bra siliensis. CD4(+), CD62L-high, and CD62L-low T cell populations from u ninfected TL-4R alpha(-/-) mice were isolated by cell sorting, Upon pr imary stimulation by T cell receptor cross-linkage, the CD62L-low, bur not the CD62L-high, cells secreted considerable amounts of IL-4, whic h was strikingly enhanced upon 4-day culture with anti-CDS in the pres ence or absence of IL-4. CD62L-low cells isolated from IL-4R alpha(-/- ), beta(2)-microglobulin(-/-) double homozygous mice produced less IL- 4 than did either IL-4R alpha(-/-) or wild-type mice. These results in dicate that an IL-4-independent, beta(2)-microglobulin-dependent pathw ay exists through which tile CD62L-low CD4(+) population has acquired IL-4-producing capacity in vivo, strongly suggesting that these cells are NK T cells.