Induction of Hyporesponsiveness and Impaired T Lymphocyte Activation by the CD31 Receptor:Ligand Pathway in T Cells

• Published in: The Journal of immunology (1950) 2001-02, Vol.166 (4), p.2364-2371
• Main Authors: Prager, Elisabeth, Staffler, Gunther, Majdic, Otto, Saemann, Marcus D, Godar, Samuel, Zlabinger, Gerhard J, Stockinger, Hannes
• Format: Article
• Language: English
• Subjects: Abatacept; Animals; Antigens, CD; Antigens, Differentiation - biosynthesis; CD31 antigen; CD31L protein; CD4 Antigens - biosynthesis; Cell Line; CHO Cells; Clonal Anergy - genetics; Clone Cells; Cricetinae; CTLA-4 Antigen; Cytokines - antagonists & inhibitors; Cytokines - biosynthesis; Down-Regulation - genetics; Down-Regulation - immunology; Gene Transfer Techniques; Humans; Immune Tolerance - genetics; Immunoconjugates; Immunosuppressive Agents - antagonists & inhibitors; Immunosuppressive Agents - metabolism; Immunosuppressive Agents - pharmacology; Ligands; Lymphocyte Activation - genetics; Platelet Endothelial Cell Adhesion Molecule-1 - biosynthesis; Platelet Endothelial Cell Adhesion Molecule-1 - blood; Platelet Endothelial Cell Adhesion Molecule-1 - genetics; Platelet Endothelial Cell Adhesion Molecule-1 - physiology; Signal Transduction - genetics; Signal Transduction - immunology; T-Lymphocytes - immunology; T-Lymphocytes - metabolism; T-Lymphocytes, Helper-Inducer - immunology; T-Lymphocytes, Helper-Inducer - metabolism; Transduction, Genetic
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.166.4.2364

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.