PRESENCE IN PERIPHERAL-BLOOD OF HEALTHY-INDIVIDUALS OF AUTOREACTIVE T-CELLS TO A MEMBRANE ANTIGEN PRESENT ON BONE-MARROW-DERIVED CELLS

Intrathymic clonal deletion is thought to be the major mechanism respo nsible for tolerance to nonsequestered antigens such as the ones expre ssed by bone marrow-derived cells. In the case of sequestered antigens that potentially do not come in contact with T cells in the thymus, i t is thought that autoreactive T cells are present in periphery but ar e tightly regulated to prevent autoimmune diseases. Indeed, autoreacti ve T cells to sequestered antigens can be isolated in healthy individu als. However, the presence of autoreactive T cells to nonsequestered c irculating 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 an tigen present on bone marrow-derived cells that is expressed on circul ating platelets and on the cell surface of the epithelial cells of the thymic stroma early in intrauterine life. Using an in vitro T-cell pr oliferation assay, we have demonstrated that activation of these speci fic GpIIb-IIIa autoreactive alpha beta TCR(+) CD4(+)CD8(-) T cells req uires internalization and processing of the GpIIb-IIia by antigen-pres enting cells and its presentation by HLA-DR class II molecules in the presence of exogenous interleukin 2 (IL-2), This indicates that some a utoreactive T cells directed against membrane antigens present on bone marrow-derived cells and also expressed in the thymus are not necessa rily eliminated by intrathymic deletion. (C) 1996 by The American Soci ety of Hematology.