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International Immunology Advance Access published online on August 16, 2006
International Immunology, doi:10.1093/intimm/dxl073
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© The Japanese Society for Immunology. 2006. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org
Received June 19, 2006
Accepted July 6, 2006

Article

CD1d-restricted NKT cell activation enhanced homeostatic proliferation of CD8+ T cells in a manner dependent on IL-4

Naoko Ueda 1, Hiroko Kuki 1, Daisuke Kamimura 2, Shinichiro Sawa 1, Kenichiro Seino 3, Takuya Tashiro 3, Ken-ichi Fushuku 3, Masaru Taniguchi 3, Toshio Hirano 2, and Masaaki Murakami 1 *

1 Laboratory of Developmental Immunology, Graduate School of Medicine and Graduate School of Frontier Biosciences, Osaka University, 565-0871 Osaka, Japan
2 Laboratory of Developmental Immunology, Graduate School of Medicine and Graduate School of Frontier Biosciences, Osaka University, 565-0871 Osaka, Japan; Laboratory for Cytokine Signaling, RIKEN Research Center for Allergy and Immunology (RCAI), 230-0045 Yokohama, Japan
3 Laboratory for Immune Regulation, RIKEN Research Center for Allergy and Immunology (RCAI), 230-0045 Yokohama, Japan

* To whom correspondence should be addressed.
Masaaki Murakami, E-mail: murakami{at}molonc.med.osaka-u.ac.jp


  Abstract

CD1d-restricted NKT cells are activated by TCR-mediated stimulation via CD1d plus lipid antigens such as alpha-galactosylceramide ({alpha}-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 {alpha}-GalCer enhanced homeostatic proliferation of CD8+ but not CD4+ T cells and this effect of {alpha}-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-4R{alpha} 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-4R{alpha} 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.

Keywords: NKT cells; homeostatic proliferation; CD8+ T cells; IL-4.
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