Nature Immunology4, 361 - 365 (2003)
Published online: 17 March 2003; | doi:10.1038/ni912
Dynamic programming of CD8+ T lymphocyte responses
Marianne J.B. van Stipdonk1, Gijs Hardenberg2, Martijn S. Bijker1, Edward E. Lemmens3, Nathalie M. Droin3, Douglas R. Green3
& Stephen P. Schoenberger3
1
Present addresses: Department of Immunohematology and Blood Transfusion, at the Leiden University Medical Center, 2333 ZA Leiden, The Netherlands.
2
Department of Clinical Oncoloy, at the Leiden University Medical Center, 2333 ZA Leiden, The Netherlands.
3
Division of Cellular Immunology, La Jolla Institute for Allergy and Immunology, San Diego, CA 92024, USA.
Correspondence should be addressed to Stephen P. Schoenberger sps@liai.org
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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