CD4+ T Cell-Derived IL-2 Signals during Early Priming Advances Primary CD8+ T Cell Responses
Open Access
- 10 November 2009
- journal article
- research article
- Published by Public Library of Science (PLoS) in PLOS ONE
- Vol. 4 (11), e7766
- https://doi.org/10.1371/journal.pone.0007766
Abstract
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-2Rβγ of CD8+ cells, which is independent of IL-2Rα. 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 IFNγ 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.Keywords
This publication has 49 references indexed in Scilit:
- Interleukin-2 signals during priming are required for secondary expansion of CD8+ memory T cellsNature, 2006
- Cognate CD4+ T cell licensing of dendritic cells in CD8+ T cell immunityNature Immunology, 2004
- Synthesis of several chemokines but few cytokines by primed uncommitted precursor CD4 T cells suggests that these cells recruit other immune cells without exerting direct effector functionsEuropean Journal of Immunology, 2004
- Homeostatic control of lymphocyte survival: potential origins and implicationsNature Immunology, 2002
- CD28/B7 SYSTEM OF T CELL COSTIMULATIONAnnual Review of Immunology, 1996
- Interleukin-2 receptor α chain regulates the size and content of the peripheral lymphoid compartmentImmunity, 1995
- Normal clonal expansion but impaired Fasmediated cell death and anergy induction in interleukin‐2‐deficient miceEuropean Journal of Immunology, 1995
- Viral induction of co-stimulatory activity on antigen-presenting cells bypasses the need for CD4+ T-cell help in CD8+ T-cell responsesCurrent Biology, 1994
- Normal development and function of CD8+ cells but markedly decreased helper cell activity in mice lacking CD4Nature, 1991
- Three‐cell‐type clusters of T cells with antigen‐presenting cells best explain the epitope linkage and noncognate requirements of the in vivo cytolytic responseEuropean Journal of Immunology, 1987