Studies on interference with tolerance induction in T cells.

The mechanism of T-cell tolerance to a thymus-dependent antigen was examined, using the adjuvant polyadenylic-polyuridylic acid (poly A:U). In adoptive transfer experiments, thymus cells obtained from donor mice 2 days after treatment with a tolerogenic dose of bovine gamma-globulin (sBGG) did not cooperate with bone marrow (BM) cells in irradiated recipients challenged with aggregated BGG (aBGG). In contrast, thymus cells from donors given sBGG plus poly A:U retained their helper activity, as assayed by hemagglutination and rosette formation of spleen cells. The effect of poly A:U in preventing tolerance induction was also demonstrable in the cortisone-resistant population, in that thymus cells from cortisone-treated donors that had received sBGG and poly A:U retained their helper function. The presence of suppressor cells and the effect of poly A:U on their stimulation were also examined. sBGG-treated thymus cells suppressed the response of BGG-primed spleen cells in lethally irradiated mice, whereas thymus cells from donors treated with sBGG and poly A:U were not suppressive. These observations show that poly A:U prevents tolerance induction and the development of suppressor activity in T cells.