CD4(+) T cells stimulate memory CD8(+) T cell expansion via acquired pMHC I complexes and costimulatory molecules, and IL-2 secretion.

The rapid and efficient expansion of CD8(+) memory T cells after the second encounter with a pathogen constitutes a hallmark trait of adaptive immunity. Yet, the contribution of CD4(+) T cells to the expansion of memory CD8(+) T cells remains the subject of controversy. Here, we show that, antigen-specific CD4(+) T cells, once activated by dendritic cells (DC) in vitro, have the capacity to stimulate expansion of memory CD8(+) T cells in vivo. The memory CD8(+) T cell expansion triggered by active CD4(+) T cells are mediated through DC-derived MHC I/peptide complexes and CD80 molecules displayed on the active CD4(+) T cells, with the involvement of IL-2 secreted by the active CD4(+) T cells. These results highlight a previously undescribed role of active CD4(+) T cells in triggering expansion of memory CD8(+) T cells.