Mc. Filion et al., PRESENCE IN PERIPHERAL-BLOOD OF HEALTHY-INDIVIDUALS OF AUTOREACTIVE T-CELLS TO A MEMBRANE ANTIGEN PRESENT ON BONE-MARROW-DERIVED CELLS, Blood, 88(6), 1996, pp. 2144-2150
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.