Abstract
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.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Abatacept
-
Animals
-
Antigens, CD
-
Antigens, Differentiation / biosynthesis
-
CD4 Antigens / biosynthesis
-
CHO Cells
-
CTLA-4 Antigen
-
Cell Line
-
Clonal Anergy / genetics
-
Clone Cells
-
Cricetinae
-
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
Substances
-
Antigens, CD
-
Antigens, Differentiation
-
CD4 Antigens
-
CTLA-4 Antigen
-
CTLA4 protein, human
-
Cytokines
-
Immunoconjugates
-
Immunosuppressive Agents
-
Ligands
-
Platelet Endothelial Cell Adhesion Molecule-1
-
Abatacept