Gamma chain required for naïve CD4+ T cell survival but not for antigen proliferation.
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 (gamma c). Using monoclonal populations of antigen-specific CD4+ T cells, we found that naïve T cells cannot survive without gamma c, whereas memory T cells show no such requirement. In contrast, neither naïve nor gamma c-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 gamma c-dependent cytokines as T cell growth factors and show that naïve and memory CD4+ T cell survival is maintained by distinct mechanisms.
Lantz
O
O
INSERM U25, Hopital Necker, Paris, France.
Grandjean
I
I
Matzinger
P
P
Di Santo
J P
JP
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002470:Cell Survival / Q000276:immunology; D004268:DNA-Binding Proteins / Q000235:genetics / Q000276:immunology*; D007156:Immunologic Memory; D051379:Mice; D008822:Mice, Transgenic; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000235:genetics / Q000276:immunology*
D004268:DNA-Binding Proteins; C499308:Rag2 protein, mouse; D016692:Receptors, Antigen, T-Cell, gamma-delta; C064655:V(D)J recombination activating protein 2