AUTOREACTIVE T-CELLS IN HEALTHY-INDIVIDUALS SHOW TOLERANCE IN-VITRO WITH CHARACTERISTICS SIMILAR TO BUT DISTINCT FROM CLONAL ANERGY

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.