Interleukin-2 enhances CD4+ T cell memory by promoting the generation of IL-7Rα-expressing cells

Abstract

The common γ chain cytokines interleukin (IL)-2 and IL-7 are important regulators of T cell homeostasis. Although IL-2 is implicated in the acute phase of the T cell response, IL-7 is important for memory T cell survival. We asked whether regulated responsiveness to these growth factors is determined by temporal expression of the cytokine-specific IL-2 receptor (R) α and IL-7Rα chains. We demonstrate that IL-2Rα is expressed early after priming in T cell receptor-transgenic CD4+ T cells, whereas IL-7Rα expression is lost. In the later stage of the response, IL-7Rα is reexpressed while IL-2Rα expression is silenced. This reciprocal pattern of IL-2Rα/IL-7Rα expression is disturbed when CD4+ T cells are primed in the absence of IL-2 signals. Primed IL-2?/? or CD25?/? (IL-2Rα?/?) CD4 + T cells, despite showing normal induction of activation markers and cell division, fail to reexpress IL-7Rα late in the response. Because the generation of CD4+ memory T cells is dependent on IL-7-IL-7Rα interactions, primed IL-2?/? or CD25?/? CD4+ T cells develop poorly into long-lived memory cells. Retrovirus-mediated expression of IL-7Rα in IL-2?/? T cells restores their capacity for long-term survival. These results identify IL-2 as a factor regulating IL-7Rα expression and, consequently, memory T cell homeostasis in vivo. JEM © The Rockefeller University Press.