title: Presence in peripheral blood of healthy individuals of autoreactive T cells to a membrane antigen present on bone marrow-derived cells.
abstract: Intrathymic clonal deletion is thought to be the major mechanism responsible for tolerance to nonsequestered antigens such as the ones expressed by bone marrow-derived cells. In the case of sequestered antigens that potentially do not come in contact with T cells in the thymus, it is thought that autoreactive T cells are present in periphery but are tightly regulated to prevent autoimmune disease. Indeed, autoreactive T cells to sequestered antigens can be isolated in healthy individuals. However, the presence of autoreactive T cells to nonsequestered circulating antigens had not been observed. In this report, we present evidence for the presence, in the periphery of all healthy individuals tested (n = 25), of autoreactive T cells to GpIIb-IIIa, a membrane antigen present on bone marrow-derived cells that is expressed on circulating platelets and on the cell surface of the epithelial cells of the thymic stroma early in intrauterine life. Using an in vitro T-cell proliferation assay, we have demonstrated that activation of these specific GpIIb-IIIa autoreactive alpha beta TCR+ CD4+ CD8- T cells requires internalization and processing of the GpIIb-IIIa by antigen-presenting cells and its presentation by HLA-DR class II molecules in the presence of exogenous interleukin 2 (IL-2). This indicates that some autoreactive T cells directed against membrane antigens present on bone marrow-derived cells and also expressed in the thymus are not necessarily eliminated by intrathymic deletion.
authors.affiliation: Department of Microbiology and Immunology, Université of Montréal, Canada.
authors.forename: M C
authors.initials: MC
authors.lastname: Filion
authors.forename: C
authors.initials: C
authors.lastname: Proulx
authors.forename: A J
authors.initials: AJ
authors.lastname: Bradley
authors.forename: D V
authors.initials: DV
authors.lastname: Devine
authors.forename: R P
authors.initials: RP
authors.lastname: Sékaly
authors.forename: F
authors.initials: F
authors.lastname: Décary
authors.forename: P
authors.initials: P
authors.lastname: Chartrand
mesh_terms: D000938:Antigen-Presenting Cells / Q000276:immunology; D000954:Antigens, Surface / Q000276:immunology; D001324:Autoantigens / Q000276:immunology*; D015551:Autoimmunity; D001853:Bone Marrow / Q000276:immunology*; D001854:Bone Marrow Cells; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002462:Cell Membrane / Q000276:immunology; D004705:Endocytosis; D006684:HLA-DR Antigens / Q000276:immunology; D006801:Humans; D008213:Lymphocyte Activation; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000276:immunology*; D015375:Receptors, Interleukin-2 / Q000378:metabolism
chemical_list: D000954:Antigens, Surface; D001324:Autoantigens; D006684:HLA-DR Antigens; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D015375:Receptors, Interleukin-2