CD40 ligation in vivo induces bystander proliferation of memory phenotype CD8 T cells

Injection of agonistic anti-CD40 Abs into mice has been shown to amplify weak CD8 T cell responses to poorly immunogenic compounds and to convert T cell tolerance to T cell priming. In this study we demonstrate that anti-CD40 treatment of C57BL/6 mice, without Ag delivery, led to a marked increase in the number of memory phenotype CD4 and CD8 T cells. Adoptive transfer experiments using CD40-deficient hosts further revealed that the proliferative response of memory T cells, induced by systemic CD40 signaling, was dependent on CD40 expression of host APCs. CD40 ligation in vivo induced vigorous cell division of both memory phenotype and bona fide virus-specific memory CD8 T cells in a partially IL-15-dependent manner. However, only memory phenotype, but not Ag-experienced memory CD8 T cells increased in cell number after anti-CD40 treatment in vivo. Taken together our data show that activation of APC via CD40 induces a marked bystander proliferation of memory phenotype T cells. In addition, we demonstrate that bona fide Ag-experienced memory CD8 T cells respond differently to anti-CD40-induced signals than memory phenotype CD8 T cells.