title: Human CD4+ T cells proliferate to HLA-DR+ allogeneic vascular endothelium. Identification of accessory interactions.
abstract: Serially passaged human endothelial cell (EC) cultures will stimulate highly purified peripheral blood CD4+ T cells to proliferate if and only if the EC cultures are pretreated with IFN-gamma to induce de novo expression of MHC class II molecules, principally HLA-DR. HLA-DR-expressing EC alone appear sufficient to stimulate purified CD4+ T cell proliferation without the involvement of other leukocyte populations, as indicated by the following observations: (1) we find no contaminating leukocytes in our EC cultures by FACS analysis or fluorescence microscopy; specifically, there are no detectable CD45 or HLA-DR expressing cells; (2) neither the EC cultures nor the purified CD4+ T cells contain HLA-DR expressing cells detectable by polymerase chain reaction (PCR) of reverse-transcribed mRNA; (3) the stimulatory capacity of the EC cultures is maintained through serial subculture and through low-density replating, indicating that the stimulatory cell type must proliferate in culture as well as EC; and (4) in contrast to MLRs, the response to EC cultures is not inhibited by pretreatment of the stimulator cells and/or responding T cells with the monocyte toxin L-leucine-O-methyl ester. We have used mAb to investigate the role of various EC and T cell surface molecules in the T cell response. mAb to HLA-DR and CD4 inhibit proliferative responses of CD4+ T cells to EC cultures, as would be expected if T cells recognize and proliferate to IFN-gamma-induced allogeneic class II MHC molecules; whereas, also as expected, mAb to class I MHC molecules were without effect. Proliferation is also inhibited by mAbs to T cell CD2 and LFA-1 beta chain (CD18) and by mAbs to LFA-3 (CD58) and CD44, which are expressed by T cells and EC. mAb to ICAM-1 (CD54, a ligand for LFA-1) provides inconsistent inhibition, and mAb to ICAM-2, used with or without anti-ICAM-1, is not inhibitory. Because both of these mAb block adhesion of LFA-1 expressing T cells to EC, our data suggest that additional ligands for LFA-1 must be important for allogeneic proliferation. mAb to VLA-4 alpha or beta chains (CD49d, CD29) enhance proliferation, presumably through direct costimulation of the T cells by these antibodies. However, a mAb to VCAM-1, an EC ligand for VLA-4, is partially inhibitory.(ABSTRACT TRUNCATED AT 400 WORDS)
authors.affiliation: Department of Vascular Biology and Section of Transplantation Biology, Clinical Research Center, Harrow, U.K.
authors.forename: C O
authors.initials: CO
authors.lastname: Savage
authors.forename: C C
authors.initials: CC
authors.lastname: Hughes
authors.forename: B W
authors.initials: BW
authors.lastname: McIntyre
authors.forename: J K
authors.initials: JK
authors.lastname: Picard
authors.forename: J S
authors.initials: JS
authors.lastname: Pober
mesh_terms: D000911:Antibodies, Monoclonal / Q000494:pharmacology; D015703:Antigens, CD / Q000276:immunology*; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology; D018801:CD2 Antigens; D015704:CD4 Antigens / Q000276:immunology*; D018968:CD58 Antigens; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000276:immunology*; D005434:Flow Cytometry; D006684:HLA-DR Antigens / Q000096:biosynthesis / Q000276:immunology*; D015395:Histocompatibility Antigens Class I / Q000096:biosynthesis / Q000276:immunology; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects; D008562:Membrane Glycoproteins / Q000276:immunology; D016133:Polymerase Chain Reaction; D011971:Receptors, Immunologic / Q000276:immunology; D011994:Recombinant Proteins; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology*; D014184:Transplantation, Homologous; D014471:Umbilical Veins
chemical_list: D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D018801:CD2 Antigens; D015704:CD4 Antigens; D018968:CD58 Antigens; D006684:HLA-DR Antigens; D015395:Histocompatibility Antigens Class I; D008562:Membrane Glycoproteins; D011971:Receptors, Immunologic; D011994:Recombinant Proteins; D007371:Interferon-gamma