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Selenko-Gebauer, N; Majdic, O; Szekeres, A; Höfler, G; Guthann, E; Korthäuer, U; Zlabinger, G; Steinberger, P; Pickl, WF; Stockinger, H; Knapp, W; Stöckl, J.
B7-H1 (programmed death-1 ligand) on dendritic cells is involved in the induction and maintenance of T cell anergy.
J Immunol. 2003; 170(7):3637-3644 Doi: 10.4049/jimmunol.170.7.3637 [OPEN ACCESS]
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Co-authors Med Uni Graz
Höfler Gerald
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Abstract:
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.
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Animals -
Antibodies, Blocking - metabolism
Antibodies, Monoclonal - metabolism
Antigens, CD - metabolism
Antigens, CD80 - biosynthesis
Apoptosis - immunology
Binding Sites, Antibody - immunology
Blood Proteins - biosynthesis
Cells, Cultured - biosynthesis
Clonal Anergy - immunology
Coculture Techniques - immunology
Cytokines - biosynthesis
Dendritic Cells - immunology
Epithelial Cells - immunology
Humans - immunology
Immunosuppressive Agents - antagonists and inhibitors
Interleukin-10 - antagonists and inhibitors
Ligands - antagonists and inhibitors
Membrane Glycoproteins - antagonists and inhibitors
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Organ Specificity - immunology
Peptides - immunology
T-Lymphocytes - cytology
Th1 Cells - immunology

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