CD4+ T cell-derived IL-2 signals during early priming advances primary CD8+ T cell responses.

• Main Authors: Yo-Ping Lai, Chia-Ching Lin, Wan-Jung Liao, Chih-Yung Tang, Shu-Ching Chen
• Format: Article
• Language: English
• Published: Public Library of Science (PLoS) 2009-11-01
• Series: PLoS ONE
• Online Access: http://europepmc.org/articles/PMC2770320?pdf=render

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.