title: IL-7 reverses NK1+ T cell-defective IL-4 production in the non-obese diabetic mouse.
abstract: Converging data suggest an important role for IL-7 in T lymphocyte maturation as illustrated by the severe T lymphopenia observed in IL-7-deficient mice. We recently reported that IL-7 preferentially promotes the in vitro expansion of a discrete MHC class I-dependent lymphocyte subset comprising both CD4+ and CD4-CD8- TCR alpha beta + cells bearing several NK cells markers such NK1.1 and Ly-49. These T cells, designated as NK1+ T cells, have the unique property among thymocytes of producing large amounts of IL-4 upon primary stimulation via the TCR. We have further demonstrated that thymic NK1+ T cells of non-obese diabetic (NOD) mice, a spontaneous model of autoimmune type I diabetes, are markedly deficient in maturation both quantitatively and functionally (IL-4 production). In the present experiments, the addition of exogenous IL-7 completely restored IL-4 production by anti-TCR alpha beta-stimulated mature (HSA-CD8-) thymocytes in NOD mice. A short 2 h preincubation with IL-7 was sufficient to restore both the expression of IL-4 mRNA and IL-4 production capacity. This was related to a direct effect on NK1+ thymocytes since: (i) the effect of IL-7 was restricted to the non-mainstream MEL-14- 3G11- TCR alpha beta + subset which mostly concentrates the IL-4-producing capacity and (ii) IL-7 did not restore IL-4 production in class I-deficient mice which lack the NK1+ T cell subset. Importantly, this activity of IL-7 on NK1+ T cells was also demonstrated in non-autoimmune strains of mice. These results were extended in vivo by showing that the IL-7 treatment significantly increased the anti-CD3 triggered IL-4 production by NK1+ T spleen cells. These findings confirm the role of IL-7 in NK1+ T cell maturation and suggest that the NK1+ T cell defect in NOD mice could be related to insufficient intrathymic IL-7 bioavailability.
authors.affiliation: INSERM U 25, Hôpital Necker, Paris, France.
authors.forename: J M
authors.initials: JM
authors.lastname: Gombert
authors.forename: E
authors.initials: E
authors.lastname: Tancrède-Bohin
authors.forename: A
authors.initials: A
authors.lastname: Hameg
authors.forename: M C
authors.initials: MC
authors.lastname: Leite-de-Moraes
authors.forename: A
authors.initials: A
authors.lastname: Vicari
authors.forename: J F
authors.initials: JF
authors.lastname: Bach
authors.forename: A
authors.initials: A
authors.lastname: Herbelin
mesh_terms: D000818:Animals; D000941:Antigens / Q000032:analysis*; D000950:Antigens, Ly; D000954:Antigens, Surface / Q000032:analysis; D002454:Cell Differentiation / Q000187:drug effects; D005260:Female; D015847:Interleukin-4 / Q000819:agonists* / Q000096:biosynthesis* / Q000235:genetics; D015851:Interleukin-7 / Q000494:pharmacology*; D037181:Lectins, C-Type; D008562:Membrane Glycoproteins / Q000032:analysis*; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D016688:Mice, Inbred NOD; D055651:NK Cell Lectin-Like Receptor Subfamily B; D011506:Proteins / Q000032:analysis*; D012333:RNA, Messenger / Q000032:analysis; D055630:Receptors, NK Cell Lectin-Like; D011994:Recombinant Proteins / Q000494:pharmacology; D016176:T-Lymphocyte Subsets / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism*; D015854:Up-Regulation / Q000276:immunology*
chemical_list: D000941:Antigens; D000950:Antigens, Ly; D000954:Antigens, Surface; D015851:Interleukin-7; C527211:Klrb1c protein, mouse; D037181:Lectins, C-Type; D008562:Membrane Glycoproteins; D055651:NK Cell Lectin-Like Receptor Subfamily B; D011506:Proteins; D012333:RNA, Messenger; D055630:Receptors, NK Cell Lectin-Like; D011994:Recombinant Proteins; D015847:Interleukin-4