Expression of I-region-associated antigen (Ia) and interleukin 1 by subcultured human endothelial cells.
Activation of T cells requires three signals from an antigen-presenting cell: antigen, Ia determinants (HLA-D region determinants in man), and interleukin 1 (IL-1). Recent evidence has suggested that macrophages, dendritic cells, epidermal Langerhan's cells, and endothelial cells can each function as antigen-presenting cells (APC). If these cell types can independently function as APC, they should synthesize Ia determinants and secrete IL-1. To determine if endothelial cells fulfill these requirements, we have propagated human umbilical vein endothelial cells by serial subculture for extended periods of time and assessed Ia expression and IL-1 secretion. The endothelial cells were subcultured for 8 months (approximately 20 subcultures) and were found to display classic morphology and immunofluorescent staining for the endothelial cell-specific marker Factor VIII-related antigen. In a separate paper we have shown that these subcultured endothelial cells can present antigen to T cells in a HLA-D region-restricted fashion (C. R. Wagner, R. M. Vetto, and D. R. Burger, Subcultured human endothelial cells can independently function as fully competent antigen-presenting cells, accepted for publication, Hum. Immunol.). In this paper we present evidence demonstrating that extensively subcultured endothelial cells biosynthesize both HLA-DR and HLA-DS molecules after exposure to T cells and antigen or to a supernatant from antigen-activated T cells. Evidence is also presented that when endothelial cells are cultured in the presence of lipopolysaccharide they secrete a molecule(s) with IL-1 activity as assayed by LBRM-33-IA5 cell line production of interleukin 2.
D000938:Antigen-Presenting Cells / Q000276:immunology*; D002478:Cells, Cultured; D004727:Endothelium / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D006801:Humans; D007111:Immunity, Cellular; D007375:Interleukin-1 / Q000096:biosynthesis*; D008264:Macrophages / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology; D014680:Veins / Q000276:immunology*
D000949:Histocompatibility Antigens Class II; D007375:Interleukin-1