INFLUENCE OF A SMALL NUMBER OF MATURE T-CELLS IN DONOR BONE-MARROW INOCULA ON RECONSTITUTION OF LYMPHOID-TISSUES AND NEGATIVE SELECTION OF A T-CELL REPERTOIRE IN THE RECIPIENT

Allo-chimerism and clonal elimination of self antigen (Ag) (Ia+Mls-1(a)) reactive V beta 6(+) T cells were analyzed and compared between allogeneic bone marrow (BM) chimeras reconstituted with BM cells which had been treated with anti-Thy-1 monoclonal antibody (mAb) plus complement (C) (T- chimeras) and BM chimeras which had been reconstituted with BM cells pretreated with anti-Thy-1 mAb alone (T+ chimeras). When lethally irradiated AKR (Mls-1(a)) mice were reconstituted with BM cells from B10 or B10 H-2 congenic mice, both T+ and T- chimeras were entirely free of signs of graft-versus-host reaction (GVHR). However, complete replacement of the AKR lymphoid tissues by donor BM cells was accomplished at an early stage in T+ chimeras but not in T- chimeras. On the other hand, clonal elimination of V beta 6(+) T cells reactive to the recipient Ag (Mls-1(a)) was abolished in T+ chimeras but successfully induced in T- chimeras. The V beta 6(divided by) T cells not eliminated in T-divided by chimeras showed depressed responses against Mls-1(a) antigens. The findings herein demonstrate that T cells which contaminate a BM inoculum survive in recipient mice after treatment with anti-Thy-1 mAb without C in vitro followed by BMT. The surviving T cells have been estimated to represent fewer than 0.5% of the BM cells inoculated. These cells appear to accelerate the full replacement of recipient lymphoid tissues by donor cells. Furthermore, the T cells which survive in the marrow inoculum influence eventually the development of a tolerant state in the T cell repertoire of the donor.