IL-18 enhances IL-4 production by ligand-activated NKT lymphocytes: a pro-Th2 effect of IL-18 exerted through NKT cells.

Leite-De-Moraes MC, Hameg A, Pacilio M, Koezuka Y, Taniguchi M, Van Kaer L, Schneider E, Dy M, Herbelin A
J Immunol. 2001 166 (2): 945-51

PMID: 11145671 · DOI:10.4049/jimmunol.166.2.945

NKT cells are a remarkably versatile population whose functional capacities are determined by cytokines present in their microenvironment. In this study, we provide evidence for a new immunoregulatory effect of the proinflammatory cytokine IL-18 on NKT cells. We found that IL-18, mainly known for its involvement in NK cell activation and in Th 1 immune responses, substantially enhanced IL-4 production as well as the percentage of IL-4(+) cells among NKT lymphocytes activated by their specific ligand alpha-galactosylceramide (alpha-GalCer). The effect of IL-18 on IL-4 production by activated NKT cells took place both in vivo and in vitro and was not affected by IL-12 which increased IFN-gamma secretion in the same conditions. We show that NKT cells are the main targets for IL-18-induced IL-4 production since it occurred neither in NKT-deficient mice nor after stimulation of Th2 lymphocytes. Finally, we provide evidence that the IL-4 promptly generated by NKT cells in response to IL-18 plus alpha-galactosylceramide in vivo can effectively contribute to the adaptive Th2 immune response by up-regulating the early activation marker CD69 on B cells. Our data support the notion that, in contrast to the exclusive IFN-gamma inducer IL-12, IL-18 acts in a more subtle manner as a costimulatory factor in both pro-Th1 and pro-Th2 responses depending on the nature of the stimulation and the target cells.

MeSH Terms (20)

Adjuvants, Immunologic Animals B-Lymphocytes Cell Separation Galactosylceramides Injections, Intraperitoneal Injections, Intravenous Interferon-gamma Interleukin-4 Interleukin-18 Killer Cells, Natural Ligands Lymphocyte Activation Mice Mice, Inbred C57BL Mice, Mutant Strains Spleen T-Lymphocyte Subsets Th2 Cells Thymus Gland

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