OX40 signals preferentially mediate the generation of effector memory but not central memory CD4+ T cells (B15)

Abstract

Abstract Memory T cells can be divided into effector memory (TEM) and central memory (TCM) subsets based on their effector function and homing characteristics. Although previous studies have demonstrated that TCR and cytokine signals mediate the generation of memory T cells, it is unclear how the generation of the two memory subsets is regulated. We found that OX40-deficient mice showed a marked reduction in the number of CD4+ TEM cells, while the number of CD4+ TCM cells was normal. Adoptive transfer experiments using Ag-specific CD4+ T cells revealed that OX40 signals during the priming phase were indispensable for the optimal generation of the CD4+ TEM, but not the CD4+ TCM population. Furthermore, CD4+TEM cells that were generated in the absence of OX40 signals showed impaired cytokine production. Collectively, the present results indicate that the generation of functional CD4+TEM cells, but not TCM cells, is critically regulated by OX40 signals.