B7-H1 (programmed death-1 ligand) on dendritic cells is involved in the induction and maintenance of T cell anergy.
In an effort to identify immunoregulatory molecules on dendritic cells (DC), we generated and screened for mAbs capable of modulating the T cell stimulatory function of DC. A particularly interesting mAb was mAb DF272. It recognizes monocyte-derived DC, but not blood monocytes or lymphocytes, and has profound immunomodulatory effects on DC. Treatment of DC with intact IgG or Fab of mAb DF272 enhanced their T cell stimulatory capacity. This effect on DC was accompanied by neither an up-regulation of costimulatory molecules such as B7.1 (CD80), B7.2 (CD86), and MHC class II molecules nor by an induction of cytokine production, including IL-1, TNF-alpha, IL-10, and IL-12. Moreover, the well-established inhibitory function of IL-10-treated DC could be reverted with mAb DF272. Even T cells, anergized because of stimulation with IL-10-treated DC, could be reactivated and induced to proliferate upon stimulation with mAb DF272-treated DC. Furthermore, mAb DF272-treated DC favored the induction of a type-1 cytokine response in T cells and inhibited IL-10 production. By using a retrovirus-based cDNA expression library generated from DC, we cloned and sequenced the mAb DF272-defined cell surface receptor and could demonstrate that it is identical with B7-H1 (programmed death-1 ligand), a recently identified new member of the B7 family of costimulatory molecules. Our results thus demonstrate that the mAb DF272-defined surface molecule B7-H1 represents a unique receptor structure on DC that might play a role in the induction and maintenance of T cell anergy.
Selenko-Gebauer
Nicole
N
Institute of Immunology, University of Vienna Medical School, Vienna, Austria.
Majdic
Otto
O
Szekeres
Andreas
A
Höfler
Gerald
G
Guthann
Elisabeth
E
Korthäuer
Ulf
U
Zlabinger
Gerhard
G
Steinberger
Peter
P
Pickl
Winfried F
WF
Stockinger
Hannes
H
Knapp
Walter
W
Stöckl
Johannes
J
D000818:Animals; D019138:Antibodies, Blocking / Q000378:metabolism; D000911:Antibodies, Monoclonal / Q000378:metabolism; D015703:Antigens, CD; D017209:Apoptosis / Q000276:immunology*; D018122:B7-1 Antigen / Q000096:biosynthesis / Q000276:immunology / Q000502:physiology*; D060890:B7-H1 Antigen; D001666:Binding Sites, Antibody; D001798:Blood Proteins / Q000096:biosynthesis / Q000276:immunology / Q000502:physiology*; D002478:Cells, Cultured; D017635:Clonal Anergy / Q000276:immunology*; D018920:Coculture Techniques; D016207:Cytokines / Q000096:biosynthesis; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism*; D004847:Epithelial Cells / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007166:Immunosuppressive Agents / Q000037:antagonists & inhibitors / Q000494:pharmacology; D016753:Interleukin-10 / Q000037:antagonists & inhibitors / Q000494:pharmacology; D008024:Ligands; D008562:Membrane Glycoproteins; D051379:Mice; D009928:Organ Specificity / Q000276:immunology; D010455:Peptides / Q000276:immunology / Q000502:physiology*; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism
D019138:Antibodies, Blocking; D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D018122:B7-1 Antigen; D060890:B7-H1 Antigen; D001798:Blood Proteins; C423236:CD274 protein, human; C498919:Cd274 protein, mouse; D016207:Cytokines; D007166:Immunosuppressive Agents; D008024:Ligands; D008562:Membrane Glycoproteins; D010455:Peptides; D016753:Interleukin-10