Interleukin-2 signals during priming are required for secondary expansion of CD8+ memory T cells.
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.
Williams
Matthew A
MA
Howard Hughes Medical Institute and Department of Immunology, University of Washington, Seattle, Washington 98195, USA.
Tyznik
Aaron J
AJ
Bevan
Michael J
MJ
D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D007156:Immunologic Memory / Q000187:drug effects / Q000276:immunology*; D007376:Interleukin-2 / Q000276:immunology* / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D015375:Receptors, Interleukin-2 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects
D007376:Interleukin-2; D015375:Receptors, Interleukin-2