期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2010
卷号：107
期号：1
页码：193-198
DOI：10.1073/pnas.0909945107
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：Both CD4+ T cell help and IL-2 have been postulated to "program" activated CD8+ T cells for memory cell development. However, the linkage between these two signals has not been well elucidated. Here we have studied effector and memory CD8+ T cell differentiation following infection with three pathogens (Listeria monocytogenes, vesicular stomatitis virus, and vaccinia virus) in the absence of both CD4+ T cells and IL-2 signaling. We found that expression of CD25 on antigen-specific CD8+ T cells peaked 3-4 days after initial priming and was dependent on CD4+ T cell help, likely through a CD28:CD80/86 mediated pathway. CD4+ T cell or CD25-deficiency led to normal early effector CD8+ T cell differentiation, but a subsequent lack of accumulation of CD8+ T cells resulting in overall decreased memory cell generation. Interestingly, in both primary and recall responses KLRG1high CD127low short-lived effector cells were drastically diminished in the absence of IL-2 signaling, although memory precursors remained intact. In contrast to previous reports, upon secondary antigen encounter CD25-deficient CD8+ T cells were capable of undergoing robust expansion, but short-lived effector development was again impaired. Thus, these results demonstrated that CD4+ T cell help and IL-2 signaling were linked via CD25 up-regulation, which controls the expansion and differentiation of antigen-specific effector CD8+ T cells, rather than "programming" memory cell traits.
