| First Author | Obar JJ | Year | 2010 |
| Journal | Proc Natl Acad Sci U S A | Volume | 107 |
| Issue | 1 | Pages | 193-8 |
| PubMed ID | 19966302 | Mgi Jnum | J:156498 |
| Mgi Id | MGI:4420736 | Doi | 10.1073/pnas.0909945107 |
| Citation | Obar JJ, et al. (2010) 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 107(1):193-8 |
| abstractText | 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. |
