Open AccessCD1d-restricted NKT cell activation enhanced homeostatic proliferation of CD8+ T cells in a manner dependent on IL-4
Author(s) -
Naoko Ueda,
Hiroko Kuki,
Daisuke Kamimura,
Shinichiro Sawa,
Kenichiro Seino,
Takuya Tashiro,
Ken Ichi Fushuku,
Masaru Taniguchi,
Toshio Hirano,
Masaaki Murakami
Publication year - 2006
Publication title -
international immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.86
H-Index - 134
eISSN - 1460-2377
pISSN - 0953-8178
DOI - 10.1093/intimm/dxl073
Subject(s) - natural killer t cell , cd1d , microbiology and biotechnology , biology , t cell , cd8 , cytotoxic t cell , homeostasis , zap70 , cd1 , interleukin 21 , immunology , immune system , in vitro , biochemistry
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-4Ralpha 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-4Ralpha 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.