IL-7 reverses NK1+ T cell-defective IL-4 production in the non-obese diabetic mouse

• Published in: International immunology 1996-11, Vol.8 (11), p.1751-1751
• Main Authors: Gombert, J M, Tancrède-Bohin, E, Hameg, A, Leite-de-Moraes, M C, Vicari, A, Bach, J F, Herbelin, A
• Format: Article
• Language: English
• Subjects: Animals; Antigens - analysis; Antigens, Ly; Antigens, Surface - analysis; Cell Differentiation - drug effects; Female; Interleukin-4 - agonists; Interleukin-4 - biosynthesis; Interleukin-4 - genetics; Interleukin-7 - pharmacology; Lectins, C-Type; Membrane Glycoproteins - analysis; Mice; Mice, Inbred BALB C; Mice, Inbred C3H; Mice, Inbred C57BL; Mice, Inbred NOD; NK Cell Lectin-Like Receptor Subfamily B; Proteins - analysis; Receptors, NK Cell Lectin-Like; Recombinant Proteins - pharmacology; RNA, Messenger - analysis; T-Lymphocyte Subsets - drug effects; T-Lymphocyte Subsets - immunology; T-Lymphocyte Subsets - metabolism; Up-Regulation - immunology
• ISSN: 0953-8178; 1460-2377
• DOI: 10.1093/intimm/8.11.1751

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.