DELETION OF DONOR-REACTIVE T-LYMPHOCYTES IN ADULT MICE AFTER INTRATHYMIC INOCULATION WITH LYMPHOID-CELLS

Clonal deletion of self antigen-reactive T lymphocytes is known to be a dominant mechanism of tolerance induction in the normal immune syste m. This report considers whether deletion of antigen-reactive T cells is also the immunologic basis for the recently described model of tran splantation tolerance that follows intrathymic inoculation with alloge neic lymphoid cells. We found that the outcome of injecting Mls(a-) ho sts with lymphocytes from Mls(a+) donors was depletion of Vbeta6+ T ce lls (which are known to be reactive with the Mls(a) superantigen). The process was found to be specific in that a similar reduction was not seen in an irrelevant T cell population (Vbeta8+) in IT injected hosts . Deletion was observed in this model only if immunosuppression with A LS or anti-CD4 accompanied intrathymic injection. When the inoculum of allogeneic lymphocytes was administered intravenously instead of intr athymically only minimal deletion was observed. The induction of trans plantation tolerance by intrathymic injection of donor lymphoid cells may prove especially efficacious since it relies on deletion of only t hose T cells specifically reactive to donor antigens, a process analog ous to tolerance induction to self antigens.