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Presence in peripheral blood of healthy individuals of autoreactive T cells
to a membrane antigen present on bone marrow-derived cells
MC Filion, C Proulx, AJ Bradley, DV Devine, RP Sekaly, F Decary and P Chartrand
Department of Microbiology and Immunology, Universite of Montreal, Canada.
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.
Volume 88,
Issue 6,
pp. 2144-2150,
09/15/1996
Copyright © 1996 by The American Society of Hematology
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