Proceedings of the National Academy of Sciences of the United States of America
Geisel School of Medicine
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 KLRG1(high) CD127(low) 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.
Obar JJ, Molloy MJ, Jellison ER, Stoklasek TA, Zhang W, Usherwood EJ, Lefrançois L. CD4+ T cell regulation of CD25 expression controls development of short-lived effector CD8+ T cells in primary and secondary responses. Proc Natl Acad Sci U S A. 2010 Jan 5;107(1):193-8. doi: 10.1073/pnas.0909945107. Epub 2009 Dec 4. PMID: 19966302; PMCID: PMC2806751.
Dartmouth Digital Commons Citation
Obar, Joshua J.; Molloy, Michael J.; Jellison, Evan R.; Stoklasek, Thomas A.; Zhang, Weijun; Usherwood, Edward J.; and Lefrançois, Leo, "CD4+ T Cell Regulation of CD25 Expression Controls Development of Short-Lived Effector CD8+ T Cells in Primary and Secondary Responses" (2010). Dartmouth Scholarship. 1484.