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

MA Williams, AJ Tyznik, MJ Bevan - Nature, 2006 - nature.com
Nature, 2006nature.com
Abstract Although interleukin-2 (IL-2) was initially characterized as the primary T-cell growth
factor following in vitro activation, 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,,,, attributable to the central role of IL-2 in the
generation, maintenance and function of CD4+ CD25+ regulatory T cells,,,. To bypass these
inherent difficulties, we have studied the effect of IL-2 on T-cell responses to acute infections …
Abstract
Although interleukin-2 (IL-2) was initially characterized as the primary T-cell growth factor following in vitro activation, 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,,,, attributable to the central role of IL-2 in the generation, maintenance and function of CD4+CD25+ regulatory T cells,,,. 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.
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