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Th1 Cytokine-Conditioned Bone Marrow-Derived Dendritic Cells Can Bypass the Requirement for Th Functions During the Generation of CD8⁺ CTL¹

Marimo Sato^*, Kenji Chamoto^*, Takemasa Tsuji^*, Yoichiro Iwakura, Yuji Togashi^*, Toshiaki Koda^* and Takashi Nishimura^2,*

^* Division of Immunoregulation, Institute for Genetic Medicine Hokkaido University, Sapporo, Japan; and Center for Experimental Medicine, Institute of Medical Science, University of Tokyo, Tokyo, Japan

Bone marrow-derived dendritic cell (BMDC) subsets have distinct immunoregulatory functions. Th1 cytokine-induced BMDC (BMDC1), compared with Th2 cytokine-induced BMDC2, have superior activities for the differentiation and expansion of CTL. To evaluate the cellular interactions between dendritic cells 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-induced BMDC) and BMDC2 failed to promote the differentiation of CD8⁺ CTL. Using Ab-blocking experiments and studies with gene knockout mice, IL-2 and LFA-1 are demonstrated to be critical for BMDC1-induced CTL differentiation. Unexpectedly, BMDC1 were able to induce CTL from CD8⁺ T cells isolated from IFN-^-/- and IFN- receptor^-/- mice. However, BMDC1 produced higher levels of IFN- than other BMDC subsets, and anti-IFN- mAb blocked BMDC1-dependent CTL generation. These results indicated an indispensable role of IFN-, but not IFN-, during BMDC1-induced CTL differentiation. We conclude that Th1-cytokine-conditioned BMDC1 can bypass Th cell function for the differentiation of naive CD8⁺ T cells into CTL.

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