Dynamic programming of CD8+ T lymphocyte responses

Abstract

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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Figure 1: In vitro and in vivo expansion of OT-I CTLs.
Figure 2: Abortive expansion in vivo is not overcome by overexpression of Bcl-2 or Bcl-xL.
Figure 3: Sustained antigenic stimulation leads to increased IL-2 production and IL-2 receptor-α expression.
Figure 4: Briefly stimulated CTLs show decreased cytotoxicity in vivo.

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Acknowledgements

This is manuscript no. 529 from the La Jolla Institute for Allergy and Immunology, La Jolla, CA. Supported by grants from the American Cancer Society, the National Institutes of Health, Cap CURE and the Netherlands Cancer Society.

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Correspondence to Stephen P. Schoenberger.

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The authors declare no competing financial interests.

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