CD1d-restricted NKT cell activation enhanced homeostatic proliferation of CD8+ T cells in a manner dependent on IL-4.
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.
Ueda
Naoko
N
Laboratory of Developmental Immunology, Graduate School of Medicine and Graduate School of Frontier Biosciences, Osaka University, 565-0871 Osaka, Japan.
Kuki
Hiroko
H
Kamimura
Daisuke
D
Sawa
Shinichiro
S
Seino
Kenichiro
K
Tashiro
Takuya
T
Fushuku
Ken-ichi
K
Taniguchi
Masaru
M
Hirano
Toshio
T
Murakami
Masaaki
M
D000818:Animals; D018949:Antigens, CD1 / Q000276:immunology / Q000378:metabolism*; D055610:Antigens, CD1d; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D005699:Galactosylceramides / Q000494:pharmacology; D006706:Homeostasis; D015847:Interleukin-4 / Q000276:immunology / Q000378:metabolism*; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D050800:STAT6 Transcription Factor / Q000276:immunology / Q000378:metabolism
D018949:Antigens, CD1; D055610:Antigens, CD1d; D005699:Galactosylceramides; D050800:STAT6 Transcription Factor; C493154:alpha-galactosylceramide; D015847:Interleukin-4