Invariant NKT cells biased for IL-5 production act as crucial regulators of inflammation.
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.
Sakuishi
Kaori
K
Department of Immunology, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Tokyo, Japan.
Oki
Shinji
S
Araki
Manabu
M
Porcelli
Steven A
SA
Miyake
Sachiko
S
Yamamura
Takashi
T
D000328:Adult; D000818:Animals; D000911:Antibodies, Monoclonal / Q000502:physiology; D018949:Antigens, CD1 / Q000378:metabolism; D055610:Antigens, CD1d; D017252:CD3 Complex / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D002454:Cell Differentiation / Q000276:immunology; D002999:Clone Cells; D018920:Coculture Techniques; D020869:Gene Expression Profiling; D006801:Humans; D007249:Inflammation / Q000276:immunology* / Q000378:metabolism; D019409:Interleukin-15 / Q000502:physiology; D007376:Interleukin-2 / Q000494:pharmacology / Q000502:physiology; D015848:Interleukin-5 / Q000096:biosynthesis*; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D018418:Th2 Cells / Q000276:immunology / Q000473:pathology; D015854:Up-Regulation / Q000276:immunology