Induction of hyporesponsiveness and impaired T lymphocyte activation by the CD31 receptor:ligand pathway in T cells.
CD31 is a member of the Ig superfamily expressed on various cell types of the vasculature, including a certain subpopulation of T lymphocytes. Previous reports suggest that interaction of CD31 with its heterophilic ligand on T cells (T cell CD31 ligand) plays a regulatory role in T lymphocyte activation. Here we demonstrate that a soluble rCD31-receptorglobulin (CD31Rg) specifically down-regulated the proliferation of human peripheral blood CD31(-) T lymphocytes stimulated via CD3 and CD28 mAbs. Notably, engagement of the T cell CD31 ligand by CD31Rg during primary stimulation also induced a prolonged unresponsive state in T cells. Retroviral transduction of CD31 into CD31(-) Th clones resulted in a significant inhibition of their proliferative capacity. When cocultured with purified CD31(-) T lymphocytes, irradiated CD31-transduced Th clones counterregulated the CD3/CD28-mediated activation of these cells. Furthermore, primary stimulation in the presence of CD31-transduced Th clones induced a comparable state of hyporesponsiveness in the T cell responders as the soluble CD31Rg. Thus, by counterregulating the activation of cognate T lymphocytes, CD31-expressing T cells might contribute to the establishment and maintenance of peripheral tolerance.
Prager
E
E
Institute of Immunology, Vienna International Research Cooperation Center at Novartis Forschungsinstitut, University of Vienna, Vienna, Austria.
Staffler
G
G
Majdic
O
O
Säemann
M
M
Godár
S
S
Zlabinger
G
G
Stockinger
H
H
D000069594:Abatacept; D000818:Animals; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000096:biosynthesis; D015704:CD4 Antigens / Q000096:biosynthesis; D016466:CHO Cells; D060908:CTLA-4 Antigen; D002460:Cell Line; D017635:Clonal Anergy / Q000235:genetics; D002999:Clone Cells; D006224:Cricetinae; D016207:Cytokines / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D015536:Down-Regulation / Q000235:genetics / Q000276:immunology; D018014:Gene Transfer Techniques; D006801:Humans; D007108:Immune Tolerance / Q000235:genetics; D018796:Immunoconjugates; D007166:Immunosuppressive Agents / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000494:pharmacology; D008024:Ligands; D008213:Lymphocyte Activation / Q000235:genetics; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000096:biosynthesis / Q000097:blood / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology / Q000378:metabolism; D014161:Transduction, Genetic
D015703:Antigens, CD; D000943:Antigens, Differentiation; D015704:CD4 Antigens; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; D016207:Cytokines; D018796:Immunoconjugates; D007166:Immunosuppressive Agents; D008024:Ligands; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D000069594:Abatacept