Apoptosis is necessary for functional T cell memory after influenza infection (49.19)

The Journal of Immunology(2011)

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摘要
Abstract Apoptosis can play a central role in the response to intracellular infections, both in the regulation of innate and adaptive immune responses and in the survival of the pathogen-infected cell. We investigated the effect of apoptosis in the response to influenza in various apoptosis deficient mouse models (Bim-/-, Bcl-2 and Akt tg) in vivo. Quantification of CD8 T-cells specific for immunodominant influenza epitopes (DbNP366, Db PA244, KbPB1703) revealed an increase in percentage and absolute CD8+ T cell numbers in the Akt tg, Bcl2 tg and Bim-/- primary, memory and secondary CD8+ T cell responses. The most striking effect was found in the Bim-/- model: a total ablation of the contraction phase after the CD8+ T cell response, leaving the number of flu specific memory CD8+ T cells abnormally high. Surprisingly, the immunodominance hierarchy in the memory Bim-/- response resembles that of a recall response (NP>>PA≈PB1). Their recall potential seemed blunted on a per cell basis compared to recall infections in wildtype mice, but after competitive adoptive transfer, the intrinsic recall division potential between the two memory cell populations was identical. However, Bim-/- CD8 T cells proved to be functionally deficient by cytokine production and effector activity, indicating a defect in the quality of memory. Thus, Bim-/- mediated contraction plays a role in selecting a memory precursor population with effector, rather than division, potential.
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