TY - JOUR
T1 - CD1d-restricted NKT cell activation enhanced homeostatic proliferation of CD8+ T cells in a manner dependent on IL-4
AU - Ueda, Naoko
AU - Kuki, Hiroko
AU - Kamimura, Daisuke
AU - Sawa, Shinichiro
AU - Seino, Kenichiro
AU - Tashiro, Takuya
AU - Fushuku, Ken Ichi
AU - Taniguchi, Masaru
AU - Hirano, Toshio
AU - Murakami, Masaaki
N1 - Funding Information:
We thank M. Kubo (RIKEN, Research Center for Allergy and Immunology) for providing IL-4RαKO and STAT6KO mice. We also thank KIRIN for α-GalCer. We appreciate Ms E. Iketani and Ms T. Hayashi for their excellent technical assistance and thank Ms R. Masuda and Ms M. Shimura for their excellent secretarial assistance. This work was supported by a Grant-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology in Japan; the Uehara Foundation and the Osaka Foundation for the Promotion of Clinical Immunology.
PY - 2006/9
Y1 - 2006/9
N2 - CD1d-restricted NKT cells are activated by TCR-mediated stimulation via CD1d plus lipid antigens such as alpha-galactosylceramide (α-GalCer). These cells suppressed autoimmunity and graft rejection, but sometimes enhanced resistance to infection and tumor immunity. This double-action phenomenon of NKT cells is partly explained by cytokines produced by NKT cells. Therefore, roles of cytokines from activated NKT cells have been extensively examined; however, their roles on T cell homeostatic proliferation in lymphopenic condition have not been investigated. Here, we showed that α-GalCer enhanced homeostatic proliferation of CD8+ but not CD4+ T cells and this effect of α-GalCer was required for NKT cells. IL-4 was essential and sufficient for this NKT cell action on CD8+ T cell homeostatic proliferation. Importantly, the expression of IL-4Rα and STAT6 in CD8+ T cells was essential for the NKT activity, indicating a direct action of IL-4 on CD8+ T cells. Consistent with this, the level of IL-4Rα expression on memory phenotype CD8+ T cells was higher than that on naive phenotype one and CD4+ T cells. Thus, these results showed the 'involvement' of IL-4 that is produced from activated NKT cells for CD8+ T cell homeostatic proliferation in vivo.
AB - CD1d-restricted NKT cells are activated by TCR-mediated stimulation via CD1d plus lipid antigens such as alpha-galactosylceramide (α-GalCer). These cells suppressed autoimmunity and graft rejection, but sometimes enhanced resistance to infection and tumor immunity. This double-action phenomenon of NKT cells is partly explained by cytokines produced by NKT cells. Therefore, roles of cytokines from activated NKT cells have been extensively examined; however, their roles on T cell homeostatic proliferation in lymphopenic condition have not been investigated. Here, we showed that α-GalCer enhanced homeostatic proliferation of CD8+ but not CD4+ T cells and this effect of α-GalCer was required for NKT cells. IL-4 was essential and sufficient for this NKT cell action on CD8+ T cell homeostatic proliferation. Importantly, the expression of IL-4Rα and STAT6 in CD8+ T cells was essential for the NKT activity, indicating a direct action of IL-4 on CD8+ T cells. Consistent with this, the level of IL-4Rα expression on memory phenotype CD8+ T cells was higher than that on naive phenotype one and CD4+ T cells. Thus, these results showed the 'involvement' of IL-4 that is produced from activated NKT cells for CD8+ T cell homeostatic proliferation in vivo.
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U2 - 10.1093/intimm/dxl073
DO - 10.1093/intimm/dxl073
M3 - Article
C2 - 16914507
AN - SCOPUS:33748988988
SN - 0953-8178
VL - 18
SP - 1397
EP - 1404
JO - International immunology
JF - International immunology
IS - 9
ER -