title: Major histocompatibility complex class II-expressing endothelial cells induce allospecific nonresponsiveness in naive T cells.
abstract: The role of endothelial cells (EC) in initiating a primary T cell response is of importance in clinical transplantation and autoimmunity since EC are the first allogeneic target encountered by the recipient's immune system and may display tissue-specific autoantigens in the context of an inflammatory response. In this study, we have investigated the antigen-presenting cell function of human umbilical vein-derived EC (HUVEC), depleted of constitutively major histocompatibility complex class II+ cells and induced to express class II molecules by interferon-gamma. The results show that HUVEC do not express B7 but can support proliferation by antigen-specific T cell clones. In contrast, they were unable to initiate a primary alloresponse using three independent HUVEC cultures and MHC class II-mismatched CD4+ T cells from eight donors. The response to HUVEC was reconstituted by trans-costimulation provided by DAP.3 transfectants expressing human B7.1. Coculture of peripheral blood T cells with EC expressing allogeneic DR molecules had markedly different effects on CD45RO+ and RA+ subsets. Subsequent reactivity of the RO+ T cells was unaffected by exposure to EC, indicating a neutral encounter. In contrast, culture with DR+ EC induced allospecific nonresponsiveness in RA+ T cells.
authors.affiliation: Department of Immunology, Royal Postgraduate Medical School, Hammersmith Hospital, London, United Kingdom.
authors.forename: F M
authors.initials: FM
authors.lastname: Marelli-Berg
authors.forename: R E
authors.initials: RE
authors.lastname: Hargreaves
authors.forename: P
authors.initials: P
authors.lastname: Carmichael
authors.forename: A
authors.initials: A
authors.lastname: Dorling
authors.forename: G
authors.initials: G
authors.lastname: Lombardi
authors.forename: R I
authors.initials: RI
authors.lastname: Lechler
mesh_terms: D017951:Antigen Presentation; D015703:Antigens, CD / Q000276:immunology; D051940:B7-2 Antigen; D018920:Coculture Techniques; D004730:Endothelium, Vascular / Q000166:cytology / Q000276:immunology*; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D006801:Humans; D007108:Immune Tolerance; D007371:Interferon-gamma / Q000494:pharmacology; D008562:Membrane Glycoproteins / Q000276:immunology; D016176:T-Lymphocyte Subsets; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D015703:Antigens, CD; D051940:B7-2 Antigen; C497964:CD86 protein, human; D000949:Histocompatibility Antigens Class II; D008562:Membrane Glycoproteins; D007371:Interferon-gamma