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, 2010 Jan 05.
Article
in En
| MEDLINE
| ID: mdl-19966302
ABSTRACT
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 CD28CD80/86 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.
Full text:
1
Database:
MEDLINE
Main subject:
CD4-Positive T-Lymphocytes
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CD8-Positive T-Lymphocytes
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Interleukin-2 Receptor alpha Subunit
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Immune System
Limits:
Animals
Language:
En
Year:
2010
Type:
Article