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

Abstract

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 (CD44highCD62Llow) 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.