Interleukin-2 signals during priming are required for secondary expansion of CD8(+) memory T cells

Article

关键词: LYMPHOCYTIC CHORIOMENINGITIS VIRUS;    CD8-T-CELL MEMORY;    IMMUNE-RESPONSES;    CD4-T-CELL HELP;    ACUTE INFECTION;    IL-2;    MICE;    EXPRESSION;    EFFECTOR;    GENE;   

DOI  :  10.1038/nature04790

来源: SCIE

【 摘 要 】

Although interleukin-2 (IL-2) was initially characterized as the primary T-cell growth factor following in vitro activation(1), less is known about its role in shaping T-cell responses to acute infections in vivo. The use of IL-2- or IL-2- receptor-deficient mice is problematic owing to their early development of autoimmunity(2-5), attributable to the central role of IL-2 in the generation, maintenance and function of CD4(+) CD25(+) regulatory T cells(6-9). To bypass these inherent difficulties, we have studied the effect of IL-2 on T-cell responses to acute infections by adopting a mixed chimaera strategy in which T cells lacking the high-affinity IL-2 receptor could be studied in an otherwise healthy mouse containing a full complement of regulatory T cells. Here we show that although IL-2 signalling to pathogen-specific CD8(+) T cells affects the number of developing effector and memory cells very little, it is required for the generation of robust secondary responses. This is not due to an altered T-cell-receptor repertoire development or selection, and does not reflect an acute requirement for IL-2 during secondary activation and expansion. Rather, we demonstrate a previously unappreciated role for IL-2 during primary infection in programming the development of CD8(+) memory T cells capable of full secondary expansion. These results have important implications for the development of vaccination or immunotherapeutic strategies aimed at boosting memory T-cell function.

【 授权许可】

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