Mc. Filion et al., AUTOREACTIVE T-CELLS IN HEALTHY-INDIVIDUALS SHOW TOLERANCE IN-VITRO WITH CHARACTERISTICS SIMILAR TO BUT DISTINCT FROM CLONAL ANERGY, European Journal of Immunology, 25(11), 1995, pp. 3123-3127
Peripheral tolerance to self antigens has been suspected to play an im
portant role in the regulation of the immune response in humans since
autoreactive T cells can be isolated from the peripheral blood of heal
thy individuals. The mechanism of this tolerance is not known, but a n
umber of groups have shown that autoreactive T cells can be induced to
proliferate in vitro by the addition of their specific antigen and ex
ogenous interleukin (IL)-2. In this report, we present the analysis of
autoreactive T cells, isolated from healthy individuals, to the autoa
ntigen GpIIb-IIIa present on circulating bone-marrow-derived cells and
on thymic epithelial cells. We found that the response of GpIIb-IIIa
autoreactive T cells in vitro, when stimulated with GpIIb-IIIa, shares
characteristics with the response found for anergic T cells. In respo
nse to GpIIb-IIIa, the GpIIb-IIIa-autoreactive T cells are neither abl
e to proliferate nor produce IL-2 on their own, but do express IL-2 re
ceptors alpha on their cell surface and produce IFN-gamma. This state
of unresponsiveness can be broken by the addition of exogenous IL-2 an
d IL-7, as in the case of anergic T cells. However, GpIIb-IIIa-autorea
ctive T cells differ from anergic T cells in their capacity to be stim
ulated by IL-12 and by their production of IL-2 mRNA. Interestingly, o
nce the unresponsive state to GpIIb-IIIa has been broken by the additi
on of IL-2, GpIIb-IIIa autoreactive T cells can produce IL-2 and proli
ferate when restimulated by GpIIb-IIIa alone. Altogether, these result
s suggest that the tolerance of GpIIb-IIIa autoreactive T cells from h
ealthy individuals could involve post-transcriptional regulation of IL
-2 expression.