IL-4-producing NK1.1+ T cells are resistant to glucocorticoid-induced apoptosis: implications for the Th1/Th2 balance.
To elucidate the mechanisms by which glucocorticoids promote Th2-type responses, we investigated the influence of dexamethasone (DEX) on both cytokine production and viability of NK1.1+ T cells. The in vivo administration of DEX enhanced the IL-4 production of spleen cells and liver mononuclear cells in wild-type mice, but not in beta2m-deficient mice. DEX reduced the cellularity of conventional T cells, but not that of NK1.1+ T cells, in both spleen and liver, suggesting an increased proportion of NK1.1+ T cells. Moreover, the proportion of IL-4-producing NK.1 + T cells increased in the DEX-injected mice. These results suggest that DEX induced IL-4 production through the preferential survival of IL-4-producing NKI.1+ T cells. In investigating the reason for the preferential survival of NK1.1+ T cells, we found that NK1.1+ T cells were resistant to DEX-induced apoptosis and expressed a higher level of intracellular Bcl-2 compared with conventional NKI.1- T cells. In addition, splenic and hepatic NK1.1+ T cells were resistant to radiation-induced apoptosis. Collectively, our findings revealed an important role for NK1.1+ T cells in the regulation of Th1/Th2 balance by glucocorticoids and their possible functions under various apoptotic stimuli.
Tamada
K
K
Department of Immunology, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan.
Harada
M
M
Abe
K
K
Li
T
T
Nomoto
K
K
D000818:Animals; D000941:Antigens; D000950:Antigens, Ly; D000954:Antigens, Surface; D017209:Apoptosis / Q000187:drug effects / Q000276:immunology* / Q000528:radiation effects; D017252:CD3 Complex; D002470:Cell Survival / Q000187:drug effects / Q000276:immunology; D003907:Dexamethasone / Q000494:pharmacology*; D005260:Female; D007113:Immunity, Innate / Q000187:drug effects / Q000528:radiation effects; D015847:Interleukin-4 / Q000096:biosynthesis*; D037181:Lectins, C-Type; D008099:Liver / Q000166:cytology / Q000276:immunology; D008213:Lymphocyte Activation / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D055651:NK Cell Lectin-Like Receptor Subfamily B; D011506:Proteins; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis; D016693:Receptors, Antigen, T-Cell, alpha-beta; D013154:Spleen / Q000166:cytology / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000187:drug effects / Q000378:metabolism* / Q000528:radiation effects; D018417:Th1 Cells / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology*; D019014:fas Receptor / Q000502:physiology
D000941:Antigens; D000950:Antigens, Ly; D000954:Antigens, Surface; D017252:CD3 Complex; C527211:Klrb1c protein, mouse; D037181:Lectins, C-Type; D055651:NK Cell Lectin-Like Receptor Subfamily B; D011506:Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D016693:Receptors, Antigen, T-Cell, alpha-beta; D019014:fas Receptor; D015847:Interleukin-4; D003907:Dexamethasone