CD40 activation boosts T cell immunity in vivo by enhancing T cell clonal expansion and delaying peripheral T cell deletion

In this report we show that activation of APC with an agonist anti-CD40 mAb profoundly alters the behavior of CD4 T cells in vivo. Stimulation of mice with anti-CD40 2 days before, but not 1 day after, administration of super antigen (SAg) enhanced CD4 and CD8 T cell clonal expansion by approximately threefold. Further, CD40 activation also delayed peripheral T cell deletio n after activation. Dying, activated T cells were quantitated by detecting extracellular phosphatidylserine with concomitant staining for SAg-reactive T cells using a TCR V beta-specific mAb, Upon close examination, it was sh own that CD40 activation delayed the death of the activated T cells. Additi onally, it was found that enhanced survival of CD4 T cells was equally depe ndent on APC expression of B7-1 and B7-2, This is in contrast to CD8 T cell s, which did not depend as much on B7-1 as B7-2, Thus, CD40 activation indi rectly promotes T cell growth and delays the death of SAg-stimulated CD4 T cells in vivo. These data suggest that one way CD40 activation promotes a m ore robust immune response is by indirectly increasing the production of ef fector T cells and by keeping them alive for longer periods of time.