title: An interleukin 4 (IL-4)-independent pathway for CD4+ T cell IL-4 production is revealed in IL-4 receptor-deficient mice.
abstract: 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.
authors.affiliation: Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892-1892, USA. nnoben@nih.gov
authors.forename: N
authors.initials: N
authors.lastname: Noben-Trauth
authors.forename: L D
authors.initials: LD
authors.lastname: Shultz
authors.forename: F
authors.initials: F
authors.lastname: Brombacher
authors.forename: J F
authors.initials: JF
authors.lastname: Urban
authors.forename: H
authors.initials: H
authors.lastname: Gu
authors.forename: W E
authors.initials: WE
authors.lastname: Paul
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism*; D018390:Gene Targeting; D015847:Interleukin-4 / Q000096:biosynthesis* / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008817:Mice, Mutant Strains; D019948:Receptors, Interleukin-4 / Q000172:deficiency / Q000235:genetics*; D018418:Th2 Cells; D001613:beta 2-Microglobulin / Q000378:metabolism
chemical_list: D019948:Receptors, Interleukin-4; D001613:beta 2-Microglobulin; D015847:Interleukin-4