γ chain required for naïve CD4+ T cell survival but not for antigen proliferation

Abstract

Lymphoid homeostasis is required to ensure immune responsiveness and to prevent immunodeficiency. As such, the immune system must maintain distinct populations of naïve T cells that are able to respond to new antigens as well as memory T cells specific to those antigens it has already encountered. Though both naïve and memory T cells reside in and traffic through secondary lymphoid organs, there is growing evidence that the two populations may be regulated differently. We show here that naïve T cell survival and memory T cell survival have different requirements for cytokines (including the interleukins IL-2, IL-4, IL-7, IL-9 and IL-15) that use the common cytokine receptor gamma chain (γc). Using monoclonal populations of antigen-specific CD4+ T cells, we found that naïve T cells cannot survive without γc, whereas memory T cells show no such requirement. In contrast, neither naïve nor γc-deficient memory T cells were impaired in their ability to proliferate and produce cytokines in response to in vivo antigenic stimulation. These data call into question the physiological role of γc-dependent cytokines as T cell growth factors and show that naïve and memory CD4+ T cell survival is maintained by distinct mechanisms.