Suppressor cells in transplantation tolerance. II. Identification and probable mode of action of chimeric suppressor T cells.

In order to differentiate between donor (chimeric F1) cells and host cells as being responsible for suppression in transplantation tolerance (TT), cells from tolerant donors were first subject to negative selection through F1 hybrid intermediate host animals. This revealed that the suppressor cells was neither completely removed from the lymph nor recoverable from the lymphoid tissues of the filter rat when highly suppressive inocula were used, suggesting that suppression did not directly depend on cells with receptors for alloantigens. The phenotype of donor and host cells in the recirculating pool was studied with fluorescent antisera and showed that both host cells and chimeric F1 cells were in the thoracic duct lymph of tolerant rats and were capable of recirculation. T and B lymphocytes of both types were present but the IgG-positive, presumptive memory B cells were highly enriched in those rapidly recirculating cells, obtained by filtration of tolerant inocula through irradiated intermediate hosts. These cells were also highly enriched for suppressor function. Methods which selectively depleted either the chimeric T cells or the B cells were applied to tolerant inocula and on adoptive transfer of these inocula, suppression was eliminated only when chimeric T cells were eliminated. This strict dependence of suppression of F1 hybrid T cells is interpreted as evidence that these cells probably suppress directly, via an anti-idiotypic mechanism, the alloreactive cells bearing idiotype-positive major histocompatibility complex receptors.