ABSTRACT
One mechanism for the induction of self-tolerance is clonal deletion of self-reactive T cells in the thymus. To be sufficient would require the absence of somatic variation of T cell receptor (TCR) genes in peripheral T cells, of extrathymic differentiation of T cells, and of any leakiness of the thymus negative selection process. Athymic nude mice of strain A were grafted with fetal thymuses of strain B. Such thymus-grafted nudes develop a normal T cell compartment and are tolerant of A and B antigens. T cells tolerant by thymic negative selection do not possess the capacity to eliminate other T cells reactive to thymic antigen in the absence of antigen expressed on non-irradiated, presumably hemopoietic cells. Moreover, CD4± T cells are not required, which is evidence against TCR-TCR interactions involving "T suppressor inducer" cells. The simple TCR-antigen interaction described in the in vitro system above leading to inhibition of CTLp recognizing CTL is also consistent with the in vivo data.
