title: Endothelial microparticles interact with and support the proliferation of T cells.
abstract: Endothelial cells closely interact with circulating lymphocytes. Aggression or activation of the endothelium leads to an increased shedding of endothelial cell microparticles (MP). Endothelial MP (EMP) are found in high plasma levels in numerous immunoinflammatory diseases, such as atherosclerosis, sepsis, multiple sclerosis, and cerebral malaria, supporting their role as effectors and markers of vascular dysfunction. Given our recently described role for human brain microvascular endothelial cells (HBEC) in modulating immune responses, we investigated how HBEC-derived MP could interact with and support the proliferation of T cells. Like their mother cells, EMP expressed molecules important for Ag presentation and T cell costimulation, that is, β2-microglobulin, MHC II, CD40, and ICOSL. HBEC were able to take up fluorescently labeled Ags with EMP also containing fluorescent Ags, suggestive of Ag carryover from HBEC to EMP. In cocultures, fluorescently labeled EMP from resting or cytokine-stimulated HBEC formed conjugates with both CD4(+) and CD8(+) subsets, with higher proportions of T cells binding EMP from cytokine-stimulated cells. The increased binding of EMP from cytokinestimulated HBEC to T cells was VCAM-1 and ICAM-1 dependent. Finally, in CFSE T cell proliferation assays using anti-CD3 mAb or T cell mitogens, EMP promoted the proliferation of CD4(+) T cells and that of CD8(+) T cells in the absence of exogenous stimuli and in the T cell mitogenic stimulation. Our findings provide novel evidence that EMP can enhance T cell activation and potentially ensuing Ag presentation, thereby pointing toward a novel role for MP in neuroimmunological complications of infectious diseases.
authors.affiliation: Vascular Immunology Unit, Discipline of Pathology, Sydney Medical School, University of Sydney, Camperdown, New South Wales 2050, Australia julie.wheway@sydney.edu.au.
authors.forename: Julie
authors.initials: J
authors.lastname: Wheway
authors.affiliation: Vascular Immunology Unit, Discipline of Pathology, Sydney Medical School, University of Sydney, Camperdown, New South Wales 2050, Australia.
authors.forename: Sharissa L
authors.initials: SL
authors.lastname: Latham
authors.affiliation: Vascular Immunology Unit, Discipline of Pathology, Sydney Medical School, University of Sydney, Camperdown, New South Wales 2050, Australia.
authors.forename: Valery
authors.initials: V
authors.lastname: Combes
authors.affiliation: Vascular Immunology Unit, Discipline of Pathology, Sydney Medical School, University of Sydney, Camperdown, New South Wales 2050, Australia.
authors.forename: Georges E R
authors.initials: GE
authors.lastname: Grau
mesh_terms: D000818:Animals; D017951:Antigen Presentation; D001921:Brain / Q000098:blood supply / Q000166:cytology / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D019013:CD40 Antigens / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D049109:Cell Proliferation; D055252:Cell-Derived Microparticles / Q000276:immunology*; D042783:Endothelial Cells / Q000166:cytology / Q000276:immunology*; D005260:Female; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D006801:Humans; D060945:Inducible T-Cell Co-Stimulator Ligand / Q000276:immunology; D008297:Male; D051379:Mice; D001613:beta 2-Microglobulin / Q000276:immunology
chemical_list: D019013:CD40 Antigens; D000949:Histocompatibility Antigens Class II; C498514:ICOSLG protein, human; D060945:Inducible T-Cell Co-Stimulator Ligand; D001613:beta 2-Microglobulin