A role for CD40 expression on CD8+ T cells in the generation of CD8+ T cell memory

The delivery of CD4 help to CD8(+) T cell responses requires interactions between CD40 and CD40 ligand and is thought to occur through antigen-presenting cell (APC) activation. Here we show that generation of memory CD8(+) T cells displaying an enhanced capacity for cell division and cytokine secretion required CD4 help but not CD40 expression by the APCs. Activated CD4(+) and CD8(+) T cells expressed CD40; and in the absence of this protein, CD8(+) T cells were unable to differentiate into memory cells or receive CD4 help. These results suggest that, like B cells, CD8(+) T cells receive CD4 help directly through CD40 and that this interaction is fundamental for CD8(+) T cell memory generation.