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Nat Immunol. 2003 Apr;4(4):361-5. Epub 2003 Mar 17.

Dynamic programming of CD8+ T lymphocyte responses.

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Division of Cellular Immunology, La Jolla Institute for Allergy and Immunology, San Diego, CA 92024, USA.


The initial encounter with an antigen-presenting cell (APC) is the primary force behind the expansion, differentiation and survival of naive T cells. Using an APC that permits temporal control of priming, we examined whether the duration of antigenic stimulation can influence the functional development of CD8+ cytotoxic T lymphocytes (CTLs) in vivo. Whereas CTLs given a 4-h stimulus underwent an abortive clonal expansion with transient surface CD25 expression, those given a 20-h stimulus sustained CD25 up-regulation, proliferated extensively, and efficiently mediated destruction of peripheral target tissues. Our results show that an instructional program preceding the first cell division integrates differences in signal strength into the decision to activate versus tolerize specific CTL clones.

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