Differential roles for OX40 and IL‐7 on homeostasis of effector memory CD4 + T cells

Homeostatic proliferation of T cells is critically involved in the generation and maintenance of memory T cells. Recent studies have focused much attention on the crucial roles of MHC‐TCR interaction and cytokines, such as IL‐7 and IL‐15, in the homeostatic control of memory CD4 + T cells. However, the role for costimulatory signals on the homeostatic proliferation of CD4 + T cells remains controversial although costimulatory signals contribute to the optimal proliferation and survival of T cells. To address the roles for signals through a T cell costimulatory molecule, OX40 on the homeostatic proliferation of effector memory CD4 + T cells, we have set up several experimental settings, in which polyclonal effector memory (CD44 high CD62L low ) CD4 + T cells were transferred into lymphopenic recipient mice. Treatment with blocking anti‐OX40L mAb during homeostatic proliferation of effector memory CD4 + T cells specifically suppressed the rapidly‐proliferating MHC II‐dependent cells. In contrast, inhibition of IL‐7 signals by administration of blocking anti‐IL‐7Rα mAb during homeostatic proliferation demonstrated a preferential reduction of the slowly‐proliferating population. Furthermore, simultaneous blockade of both OX40 and IL‐7 signals completely inhibited the homeostatic proliferation of effector memory CD4 + T cells by suppressing both the rapid and slow homeostatic proliferation. Collectively, OX40 signals contribute to the homeostasis of effector memory CD4 + T cells in an IL‐7‐independent manner. This work was supported in part by a grant‐in‐aid for scientific research from the Japan Society for the Promotion of Science.