CD4+ T cell-independent maintenance and expansion of memory CD8+ T cells derived from in vitro dendritic cell activation

CD4(+) T cells are essential for the maintenance of CD8(+) memory T (Tm) cells following acute infection, but the importance of CD4(+) T cells for the maintenance and expansion of CD8(+) Tm cells to non-infectious antigens remains mostly unknown. Here, we showed that ovalbumin (OVA)-specific CD8(+) Tm cell precursors derived from in vitro stimulation of TCR transgenic OT I CD8(+) T cells with OVA protein-pulsed bone marrow-derived dendritic cells (DCOVA) can give rise to functional CD8(+) Tm cells after adoptively transferred into mice. These CD8(+) Tm cells can be maintained and remain fully functional in CD4(+) T cell-absent environments in vivo. Furthermore, CD4(+) T cells are not essential for the expansion of these CD8(+) Tm cells. Finally, these in vitro DCOVA-activated CD8(+) Tm cells maintained in CD4-deficient mice are also able to confer fully protective immunity against a later challenge of OVA-expressing tumor cells. Collectively, these findings demonstrate that in contrast to acute infections, maintenance and expansion of CD8(+) Tm cells after priming with OVA protein-pulsed dendritic cells are independent of CD4(+) T cells.