An interleukin 4 (IL-4)-independent pathway for CD4+ T cell IL-4 production is revealed in IL-4 receptor-deficient mice.
Animal, CD4-Positive-T-Lymphocytes: me, Gene-Targeting, Interleukin-4: bi, me, Mice, Mice-Inbred-BALB-C, Mice-Mutant-Strains, Receptors-Interleukin-4: ge, df, SUPPORT-NON-U-S-GOVT, SUPPORT-U-S-GOVT-P-H-S, Th2-Cells
Proc Natl Acad Sci U S A 1997 Sep 30;94(20):10838-43
IL-4 receptor alpha chain (IL-4Ralpha)-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-4Ralpha resulted in markedly diminished, but not absent, TH2 responses after infection with the helminthic parasite Nippostrongylus brasiliensis. CD4+, CD62L-high, and CD62L-low T cell populations from uninfected IL-4Ralpha-/- mice were isolated by cell sorting. Upon primary stimulation by T cell receptor cross-linkage, the CD62L-low, but not the CD62L-high, cells secreted considerable amounts of IL-4, which was strikingly enhanced upon 4-day culture with anti-CD3 in the presence or absence of IL-4. CD62L-low cells isolated from IL-4Ralpha-/-, beta2-microglobulin-/- double homozygous mice produced less IL-4 than did either IL-4Ralpha-/- or wild-type mice. These results indicate that an IL-4-independent, beta2-microglobulin-dependent pathway exists through which the CD62L-low CD4+ population has acquired IL-4-producing capacity in vivo, strongly suggesting that these cells are NK T cells.
An interleukin 4 (IL-4)-independent pathway for CD4+ T cell IL-4 production is revealed in IL-4 receptor-deficient mice. Proc Natl Acad Sci U S A 1997 Sep 30;94(20):10838-43