Abstract
Although invariant NKT (iNKT) cells play a regulatory role in the pathogenesis of autoimmune diseases and allergy, an initial trigger for their regulatory responses remains elusive. In this study, we report that a proportion of human CD4+ iNKT cell clones produce enormous amounts of IL-5 and IL-13 when cocultured with CD1d+ APC in the presence of IL-2. Such IL-5 bias was never observed when we stimulated the same clones with alpha-galactosylceramide or anti-CD3 Ab. Suboptimal TCR stimulation by plate-bound anti-CD3 Ab was found to mimic the effect of CD1d+ APC, indicating the role of TCR signaling for selective induction of IL-5. Interestingly, DNA microarray analysis identified IL-5 and IL-13 as the most highly up-regulated genes, whereas other cytokines produced by iNKT cells, such as IL-4 and IL-10, were not significantly induced. Moreover, iNKT cells from BALB/c mice showed similar IL-5 responses after stimulation with IL-2 ex vivo or in vivo. The iNKT cell subset producing IL-5 and IL-13 could play a major role in the development of allergic disease or asthma and also in the immune regulation of Th1 inflammation.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adult
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Animals
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Antibodies, Monoclonal / physiology
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Antigens, CD1 / metabolism
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Antigens, CD1d
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CD3 Complex / immunology
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CD4-Positive T-Lymphocytes / immunology
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CD4-Positive T-Lymphocytes / metabolism
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CD4-Positive T-Lymphocytes / pathology
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Cell Differentiation / immunology
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Clone Cells
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Coculture Techniques
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Gene Expression Profiling
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Humans
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Inflammation / immunology*
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Inflammation / metabolism
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Interleukin-15 / physiology
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Interleukin-2 / pharmacology
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Interleukin-2 / physiology
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Interleukin-5 / biosynthesis*
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Killer Cells, Natural / immunology*
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Killer Cells, Natural / metabolism*
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Killer Cells, Natural / pathology
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Mice
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Mice, Inbred BALB C
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Middle Aged
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Multiple Sclerosis / immunology
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Multiple Sclerosis / metabolism
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Multiple Sclerosis / pathology
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Receptors, Antigen, T-Cell / metabolism
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T-Lymphocyte Subsets / immunology*
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T-Lymphocyte Subsets / metabolism*
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T-Lymphocyte Subsets / pathology
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Th2 Cells / immunology
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Th2 Cells / pathology
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Up-Regulation / immunology
Substances
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Antibodies, Monoclonal
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Antigens, CD1
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Antigens, CD1d
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CD1D protein, human
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CD3 Complex
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Interleukin-15
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Interleukin-2
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Interleukin-5
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Receptors, Antigen, T-Cell