High-level expression of B7-H1 molecules by dendritic cells suppresses the function of activated T cells and desensitizes allergen-primed animals.
A body of evidence indicates that expression of the programmed cell death 1 (PD-1) receptor by activated T cells plays an important role in the down-regulation of immune responses; however, the functions of its known ligands, B7-H1 (PD-L1) and B7-dendritic cell (DC; PD-L2), at the effector phase of immune responses are less clear. In the current study, we investigated the roles of B7-H1 in DC-mediated regulation of hapten-activated T cells and the delayed-type contact hypersensitivity response in primed animals. We found that the expression of B7-H1 and B7-DC was induced on activation of DC by hapten stimulation. Blockade of B7-H1, but not B7-DC, enhanced the activity of hapten-specific T cells. Interaction with a DC line that expresses high cell-surface levels of B7-H1 (B7-H1/DC) suppressed the proliferation of, and cytokine production by, activated T cells. In vivo administration of hapten-carrying B7-H1/DC desensitized the response of sensitized animals to hapten challenge, and this desensitization was hapten-specific. These data indicate that B7-H1 expressed by DC mediates inhibitory signals for activated T cells and suppresses the elicitation of immune responses. The ability of B7-H1/DC to inhibit the function of preactivated T cells in vivo suggests novel strategies for the treatment of immune response-mediated disorders.
Kim
Hee Kyung
HK
Department of Dermatology, University of Alabama at Birmingham, VH 566B, 1670 University Blvd., Birmingham, AL 35294, USA.
Guan
Hongbing
H
Zu
Guorui
G
Li
Hui
H
Wu
Lizhi
L
Feng
Xu
X
Elmets
Craig
C
Fu
Yangxin
Y
Xu
Hui
H
D000485:Allergens / Q000276:immunology*; D000818:Animals; D018122:B7-1 Antigen / Q000096:biosynthesis* / Q000276:immunology* / Q000494:pharmacology; D060890:B7-H1 Antigen; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D016207:Cytokines / Q000096:biosynthesis / Q000187:drug effects; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology*; D003888:Desensitization, Immunologic / Q000379:methods; D006241:Haptens / Q000008:administration & dosage / Q000494:pharmacology; D008024:Ligands; D008562:Membrane Glycoproteins / Q000096:biosynthesis* / Q000276:immunology* / Q000494:pharmacology; D051379:Mice; D008805:Mice, Inbred A; D008810:Mice, Inbred C57BL; D010455:Peptides / Q000276:immunology* / Q000494:pharmacology; D051381:Rats; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D013997:Time Factors; D014162:Transfection
D000485:Allergens; D018122:B7-1 Antigen; D060890:B7-H1 Antigen; C498919:Cd274 protein, mouse; D016207:Cytokines; D006241:Haptens; D008024:Ligands; D008562:Membrane Glycoproteins; D010455:Peptides