CD28 induces immunostimulatory signals in dendritic cells via CD80 and CD86.
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-gamma. Production of interleukin 6 required B7-1 (CD80), B7-2 (CD86) and p38 mitogen-activated protein kinase and prevented interferon-gamma-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.
Orabona
Ciriana
C
Department of Experimental Medicine, University of Perugia, 06126 Perugia, Italy.
Grohmann
Ursula
U
Belladonna
Maria Laura
ML
Fallarino
Francesca
F
Vacca
Carmine
C
Bianchi
Roberta
R
Bozza
Silvia
S
Volpi
Claudia
C
Salomon
Benoît L
BL
Fioretti
Maria Cristina
MC
Romani
Luigina
L
Puccetti
Paolo
P
D000818:Animals; D000906:Antibodies / Q000276:immunology / Q000494:pharmacology; D015703:Antigens, CD / Q000276:immunology*; D000970:Antineoplastic Agents / Q000276:immunology / Q000494:pharmacology; D018122:B7-1 Antigen / Q000276:immunology*; D051940:B7-2 Antigen; D018106:CD28 Antigens / Q000276:immunology*; D002177:Candidiasis / Q000188:drug therapy / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D007111:Immunity, Cellular / Q000276:immunology; D007167:Immunotherapy; D007371:Interferon-gamma / Q000276:immunology / Q000378:metabolism; D015850:Interleukin-6 / Q000276:immunology / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000276:immunology*; D051379:Mice; D009369:Neoplasms / Q000188:drug therapy / Q000276:immunology; D048051:p38 Mitogen-Activated Protein Kinases / Q000276:immunology / Q000378:metabolism
D000906:Antibodies; D015703:Antigens, CD; D000970:Antineoplastic Agents; D018122:B7-1 Antigen; D051940:B7-2 Antigen; D018106:CD28 Antigens; C497965:Cd86 protein, mouse; D015850:Interleukin-6; D008562:Membrane Glycoproteins; D007371:Interferon-gamma; D048051:p38 Mitogen-Activated Protein Kinases