The B7/BB1 antigen provides one of several costimulatory signals for the activation of CD4+ T lymphocytes by human blood dendritic cells in vitro.
T cells respond to peptide antigen in association with MHC products on antigen-presenting cells (APCs). A number of accessory or costimulatory molecules have been identified that also contribute to T cell activation. Several of the known accessory molecules are expressed by freshly isolated dendritic cells, a distinctive leukocyte that is the most potent APC for the initiation of primary T cell responses. These include ICAM-1 (CD54), LFA-3 (CD58), and class I and II MHC products. Dendritic cells also constitutively express the accessory ligand for CD28, B7/BB1, which has not been previously identified on circulating leukocytes freshly isolated from peripheral blood. Dendritic cell expression of both B7/BB1 and ICAM-1 (CD54) increases after binding to allogeneic T cells. Individual mAbs against several of the respective accessory T cell receptors, e.g., anti-CD2, anti-CD4, anti-CD11a, and anti-CD28, inhibit T cell proliferation in the dendritic cell-stimulated allogeneic mixed leukocyte reaction (MLR) by 40-70%. Combinations of these mAbs are synergistic in achieving near total inhibition. Other T cell-reactive mAbs, e.g., anti-CD5 and anti-CD45, are not inhibitory. Lymphokine secretion and blast transformation are similarly reduced when active accessory ligand-receptor interactions are blocked in the dendritic cell-stimulated allogeneic MLR. Dendritic cells are unusual in their comparably higher expression of accessory ligands, among which B7/BB1 can now be included. These are pertinent to the efficiency with which dendritic cells in small numbers elicit strong primary T cell proliferative and effector responses.
Young
J W
JW
Laboratory of Cellular Physiology and Immunology, Rockefeller University, New York 10021.
Koulova
L
L
Soergel
S A
SA
Clark
E A
EA
Steinman
R M
RM
Dupont
B
B
D000938:Antigen-Presenting Cells / Q000502:physiology; D015703:Antigens, CD / Q000502:physiology; D000945:Antigens, Differentiation, T-Lymphocyte / Q000502:physiology; D000954:Antigens, Surface / Q000502:physiology*; D018122:B7-1 Antigen; D018801:CD2 Antigens; D018106:CD28 Antigens; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D015815:Cell Adhesion Molecules / Q000032:analysis; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000502:physiology*; D006801:Humans; D018799:Intercellular Adhesion Molecule-1; D007376:Interleukin-2 / Q000378:metabolism; D007519:Isoantigens / Q000276:immunology; D008213:Lymphocyte Activation; D007959:Lymphocyte Culture Test, Mixed; D011971:Receptors, Immunologic / Q000502:physiology
D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D000954:Antigens, Surface; D018122:B7-1 Antigen; D018801:CD2 Antigens; D018106:CD28 Antigens; D015815:Cell Adhesion Molecules; D007376:Interleukin-2; D007519:Isoantigens; D011971:Receptors, Immunologic; D018799:Intercellular Adhesion Molecule-1