Bidirectional signaling along the B7–CTLA-4 coreceptor pathway enables reciprocal conditioning of T cells and dendritic cells. Although T cells can instruct dendritic cells to manifest tolerogenic properties after CTLA-4 engagement of B7, such a B7-mediated signaling is not known to occur in response to CD28. Here we show that mouse dendritic cells were induced by soluble CD28 to express interleukin 6 and interferon-γ. Production of interleukin 6 required B7-1 (CD80), B7-2 (CD86) and p38 mitogen-activated protein kinase and prevented interferon-γ-driven expression of immunosuppressive tryptophan catabolism. In vivo, an adjuvant activity of soluble CD28 was demonstrated as enhanced T cell-mediated immunity to tumor and self peptides and protection against microbial and tumor challenge. Thus, different ligands of B7 can signal dendritic cells to express functionally distinct effector responses.
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We thank V. Poli (University of Turin, Turin, Italy) for the gift of IL-6-deficient mice and G. Andrielli for technical assistance. Supported by the Italian Association for Cancer Research.
The authors declare no competing financial interests.
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Orabona, C., Grohmann, U., Belladonna, M. et al. CD28 induces immunostimulatory signals in dendritic cells via CD80 and CD86. Nat Immunol 5, 1134–1142 (2004). https://doi.org/10.1038/ni1124
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