Interaction of CD31 with a heterophilic counterreceptor involved in downregulation of human T cell responses.
CD31 is a 130-kD glycoprotein of the immunoglobulin (Ig) superfamily expressed on the surface of endothelial cells, platelets, and several leukocyte subsets. Previous reports indicated that CD31 can mediate intercellular adhesion via both homophilic and heterophilic interaction mechanisms. Using a soluble recombinant CD31-Ig fusion protein (CD31 receptor globulin [Rg]), we demonstrate here that human CD31- T lymphocytes and CD4+CD31- T cell clones express a heterophilic CD31 ligand that is upregulated 18 h after activation. Interaction of CD31Rg with CD31- T helper cell (Th) clones was divalent cation independent but could be blocked by heparin, thus indicating that the CD31 counterreceptor on T cells can be distinguished from the ligands identified on other cell types. Moreover, a single chain protein of 120 kD was precipitated by CD31Rg from the lysates of CD31- Th clones. CD31Rg completely downregulated the proliferative response and cytokine production (interleukin-4, interferon-gamma, and tumor necrosis factor-alpha) of CD31- Th clones when the cells were maximally stimulated via immobilized CD3 monoclonal antibody. These results suggest that interaction of CD31 with a heterophilic counterreceptor on T lymphocytes can interfere with a positive regulatory pathway of T cell activation, or directly signal T cells to downregulate immune function.
Prager
E
E
Institute of Immunology, Vienna International Research Cooperation Center at Sandoz Forschunginstitut, University of Vienna, Austria.
Sunder-Plassmann
R
R
Hansmann
C
C
Koch
C
C
Holter
W
W
Knapp
W
W
Stockinger
H
H
D015214:Antigens, Differentiation, Myelomonocytic / Q000502:physiology*; D001483:Base Sequence; D002413:Cations, Divalent / Q000737:chemistry; D015815:Cell Adhesion Molecules / Q000502:physiology*; D002449:Cell Aggregation; D002999:Clone Cells; D017931:DNA Primers / Q000737:chemistry; D015536:Down-Regulation; D006493:Heparin / Q000737:chemistry; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D008024:Ligands; D008213:Lymphocyte Activation; D008969:Molecular Sequence Data; D008970:Molecular Weight; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D011485:Protein Binding; D011971:Receptors, Immunologic / Q000502:physiology*; D011993:Recombinant Fusion Proteins; D013601:T-Lymphocytes / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D015214:Antigens, Differentiation, Myelomonocytic; D002413:Cations, Divalent; D015815:Cell Adhesion Molecules; D017931:DNA Primers; D008024:Ligands; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D011971:Receptors, Immunologic; D011993:Recombinant Fusion Proteins; D014409:Tumor Necrosis Factor-alpha; D015847:Interleukin-4; D007371:Interferon-gamma; D006493:Heparin