Th1 cytokine-conditioned bone marrow-derived dendritic cells can bypass the requirement for Th functions during the generation of CD8(+) CTL

Bone marrow-derived dendritic cell (BMDC) subsets have distinct immunoregul atory functions. Th1 cytokine-induced BMDC (BMDC1), compared with Th2 cytok ine-induced BMDC2, have superior activities for the differentiation and exp ansion of CTL. To evaluate the cellular interactions between dendritic cell s and CD8(+) T cells for the induction of CTL, BALB/c-derived BMDC subsets were cocultured with purified CD8(+) T cells from C57BL/6 mice. Our results demonstrate that BMDC1 support the generation of allogeneic CD8(+) CTL in the absence of CD4(+) Th cells. In contrast, BMDC0 (GM-CSF- plus IL-3-induc ed BMDC) and BMDC2 failed to promote the differentiation of CD8(+) CTL. Usi ng Ab-blocking experiments and studies with gene knockout mice, IL-2 and LF A-1 are demonstrated to be critical for BMDC1-induced CTL differentiation. Unexpectedly, BMDC1 were able to induce CTL from CD8(+) T cells isolated fr om IFN-gamma (-/-) and IFN-gamma receptor(-/-) mice. However, BMDC1 produce d higher levels of IFN-beta than other BMDC subsets, and anti-IFN-beta mAb blocked BMDC1-dependent CTL generation. These results indicated an indispen sable role of IFN-beta, but not IFN-gamma, during BMDC1-induced CTL differe ntiation. We conclude that Th1-cytokine-conditioned BMDC1 can bypass Th cel l function for the differentiation of naive CD8(+) T cells into CTL.