A role for suppressor T cells in induction of self-tolerance.

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Abstract
The potential role of suppressor T cells (Ts) in the induction of self-tolerance was investigated by eliminating I-J+ cells during ontogeny (I-J antigens are encoded by the I-J subregion of the murine major histocompatibility complex). To achieve this, F1 mice were exposed to anti-I-J antibodies via the transplancental route by mating B10.A(3R) females, preimmunized with B10.A(5R) cells, with CBA males. At 6 wk of age, the offspring were injected with rat erythrocytes (RRBC) to induce erythrocyte autoantibodies. By comparison with age-matched controls, Ts-depleted mice produced significantly higher titers of autoantibody, whereas there was no difference in the antibody response of the 2 groups to the foreign determinants on the RRBC. The selective increase in autoantibody production was mirrored at the clonal level by the appearance of self-reactive B-cell hybridomas after fusion of RRBC-immune spleen cells with the NS-1 cell line. When helper cell function of RRBC-primed cells was measured in a T-cell proliferative assay, Ts depletion in utero resulted in enhanced T-cell activity to nonself (RRBC) but not to self (mouse erythrocyte) determinants. Thus, helper T cells recognizing nonself determinants on RRBC appeared to be responsible for activating self-specific B cells, presumably through linked recognition of different epitopes on mouse erythrocytes. Taken together, these findings indicate that elimination of I-J+ cells during ontogeny can lead to the appearance and activation of forbidden B-cell clones and points to a central role for Ts in induction as well as maintenance of self-tolerance.