Nature Immunology5, 1134 - 1142 (2004)
Published online: 3 October 2004; | doi:10.1038/ni1124
CD28 induces immunostimulatory signals in dendritic cells via CD80 and CD86
Ciriana Orabona1, Ursula Grohmann1, Maria Laura Belladonna1, Francesca Fallarino1, Carmine Vacca1, Roberta Bianchi1, Silvia Bozza1, Claudia Volpi1, Benoît L Salomon2, Maria Cristina Fioretti1, Luigina Romani1
& Paolo Puccetti1
1
Department of Experimental Medicine, University of Perugia, 06126 Perugia, Italy.
2
Centre National de la Recherche Scientifique UMR 7087, Hôpital Pitié-Salpêtrière, 75013 Paris, France.
Correspondence should be addressed to Paolo Puccetti plopcc@tin.it
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-. Production of interleukin 6 required B7-1 (CD80), B7-2 (CD86) and p38 mitogen-activated protein kinase and prevented interferon--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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. Production of interleukin 6 required B7-1 (CD80), B7-2 (CD86) and p38 mitogen-activated protein kinase and prevented interferon-
