Journal
JOURNAL OF CLINICAL INVESTIGATION
Volume 108, Issue 6, Pages 871-878Publisher
AMER SOC CLINICAL INVESTIGATION INC
DOI: 10.1172/JCI13296
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Funding
- NHLBI NIH HHS [HL-56949, R01 HL054936, P01 HL056949, HL-54936] Funding Source: Medline
- NIAID NIH HHS [AI-5911, AI-46566, R01 AI045406, AI-45025, R01 AI046566, R21 AI046566, R01 AI045025, AI-45406] Funding Source: Medline
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The lineage relationship between short-lived effector T cells and long-lived memory cells is not fully understood. We have described T-GFP mice previously, in which naive and early activated T cells express GFP uniformly, whereas cells that have differentiated into effector cytotoxic T cells selectively lose GFP expression. Here we studied antigen-specific CD8 T cell differentiation using T GFP mice crossed to the TCR transgenic (Tg) mice P14 (specific for the lymphocytic choriomeningitis virus glycoprotein peptide, gp33-41). After activation with antigenic peptide, P14XT-GFP CD8(+) T cells cultured in high-dose IL-2 developed into cells with effector phenotype and function: they were blastoid, lost GFP expression, expressed high levels of activation and effector markers, and were capable of immediate cytotoxic function. In contrast, cells cultured in IL-15 or low-dose IL-2 never developed into full-fledged effector cells. Rather, they resembled memory cells: they were smaller, were GFP(+), did not express effector markers, and were incapable of immediate cytotoxicity. However, they mediated rapid-recall responses in vitro. After adoptive transfer, they survived in vivo for at least 10 weeks and mounted a secondary immune response after antigen rechallenge that was as potent as endogenously generated memory cells. In addition to providing a simple means to generate memory cells in virtually unlimited numbers, our results suggest that effector differentiation is not a prerequisite for memory cell generation.
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