Irreversible inactivation of activated cytotoxic T lymphocyte precursor cells by "anti-self" suppressor cells present in murine bone marrow T cell colonies.

When added to a mixed lymphocyte culture, cells in T cell colonies grown from bone marrow (BM) suppressed the development of cytotoxic activity against H-2 antigens shared by the colony cells and the stimulator cells, apparently by inactivating cytotoxic T lymphocyte precursor cells (CTLP). From the point of view of the added suppressor cells, the suppression was against self-reactive cells. The suppressor cells were resistant to gamma irradiation (1500 rds) but sensitive to UV irradiation. Inactivated CTLP separated from the suppressor cells by cell sorting could not be reactivated on being recultured with fresh stimulator cells, suggesting the suppression is irreversible. There was a critical time window, extending roughly from 20 to 40 h after culture initiation, during which the suppressor cell had to be present if CTLP were to be inactivated. During the first 20 h and after 40 h of exposure to stimulator cells, CTLP were resistant to the suppressor cell. Direct experimental evidence is presented against the possibility that the suppressor cells derived from BM colonies act by augmenting the production of Lyt-2+ suppressor cells from the responder population which then produce the suppression, or that the suppressor cells interfere with an early interaction between CTLP and stimulator cells. We conclude that the suppressor cells in T cell colonies grown from BM act directly on activated CTLP and permanently inactivate them.