CD4+ T cell-derived IL-2 signals during early priming advances primary CD8+ T cell responses.
Stimulating naïve CD8+ T cells with specific antigens and costimulatory signals is insufficient to induce optimal clonal expansion and effector functions. In this study, we show that the activation and differentiation of CD8+ T cells require IL-2 provided by activated CD4+ T cells at the initial priming stage within 0-2.5 hours after stimulation. This critical IL-2 signal from CD4+ cells is mediated through the IL-2Rbetagamma of CD8+ cells, which is independent of IL-2Ralpha. The activation of IL-2 signaling advances the restriction point of the cell cycle, and thereby expedites the entry of antigen-stimulated CD8+ T-cell into the S phase. Besides promoting cell proliferation, IL-2 stimulation increases the amount of IFNgamma and granzyme B produced by CD8+ T cells. Furthermore, IL-2 at priming enhances the ability of P14 effector cells generated by antigen activation to eradicate B16.gp33 tumors in vivo. Therefore, our studies demonstrate that a full CD8+ T-cell response is elicited by a critical temporal function of IL-2 released from CD4+ T cells, providing mechanistic insights into the regulation of CD8+ T cell activation and differentiation.
Lai
Yo-Ping
YP
Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.
Lin
Chia-Ching
CC
Liao
Wan-Jung
WJ
Tang
Chih-Yung
CY
Chen
Shu-Ching
SC
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism*; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism*; D003124:Colorimetry / Q000379:methods; D007371:Interferon-gamma / Q000378:metabolism; D007376:Interleukin-2 / Q000378:metabolism*; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D008954:Models, Biological; D016196:S Phase; D015398:Signal Transduction; D013154:Spleen / Q000166:cytology; D013778:Tetrazolium Salts / Q000494:pharmacology; D013844:Thiazoles / Q000494:pharmacology; D013997:Time Factors
D007376:Interleukin-2; D013778:Tetrazolium Salts; D013844:Thiazoles; D007371:Interferon-gamma; C022616:thiazolyl blue