Presence in Peripheral Blood of Healthy Individuals of Autoreactive T Cells to a Membrane Antigen Present on Bone Marrow-Derived Cells

• Published in: Blood Vol. 88; no. 6; pp. 2144 - 2150
• Main Authors: Filion, Mario C., Proulx, Chantal, Bradley, Amanda J., Devine, Dana V., Sekaly, Rafick-Pierre, Decary, Francine, Chartrand, Pierre
• Format: Journal Article
• Language: English
• Published: Washington, DC Elsevier Inc 15-09-1996; The Americain Society of Hematology
• Subjects: Antigen-Presenting Cells - immunology; Antigens, Surface - immunology; Autoantigens - immunology; Autoimmunity; Biological and medical sciences; Bone Marrow - immunology; Bone Marrow Cells; CD4-Positive T-Lymphocytes - immunology; Cell Membrane - immunology; Endocytosis; Fundamental and applied biological sciences. Psychology; Fundamental immunology; HLA-DR Antigens - immunology; Humans; Immunobiology; Lymphocyte Activation; Lymphoid cells: ontogeny, maturation, markers, receptors, circulation and recirculation; Platelet Glycoprotein GPIIb-IIIa Complex - immunology; Receptors, Interleukin-2 - metabolism; Antigen; Human; Glycoprotein IIbIIIa; Leukocyte; T-Lymphocyte; Bone marrow; Cell surface; Blood
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.V88.6.2144.bloodjournal8862144

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 diseases. 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 Gpllb-llla, 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 Gpllb-llla autoreactive αβTCR+ CD4+CD8- T cells requires internalization and processing of the Gpllb-llla 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.