Bone marrow-derived cells are essential for intrathymic deletion of self-reactive T cells in both the host- and donor-derived thymocytes of fully allogeneic bone marrow chimeras

The fate of self-reactive T cells was examined in both the host- and donor-derived thymocytes of fully allogeneic bone marrow (BM) chimeras of two strain combinations of AKR/J (H-2(k), IE⁺, Thy-1.1, Mls-1^a2^b) and C57BL/6 (H-2^b, IE^-, Thy-1.2, Mls-1^b2^b). Sequential appearance of host- and donor-derived T cells occurred in the thymus of both AKR → B6 and B6 → AKR chimeras in which 5 x 10⁶ of T cell-depleted BM cells were used to reconstitute recipients lethally irradiated with 950 rad. Thymocytes bearing Vβ6(high), which recognize MHC class II IE-binding Ag encoded by Mls-1^a allele, were detected in neither host- nor donor-derived thymocytes of AKR-B6 chimeras in which Mls-1^a and IE were expressed only by the BM-derived cells. Thymocytes bearing Vβ11(high) capable of recognizing IE were also deleted in the host- and donor-derived thymocytes of the AKR → B6 chimeras. One million of BM cells were inadequate to deletion of the Vβ6(high) and Vβ11(high) T cells in the host-derived thymocytes of these chimeras. On the other hand, significant numbers of Vβ6(high) and Vβ11(high) thymocytes were detected in both the host- and donor-derived thymocytes in B6 → AKR chimeras where sufficient doses of IE^- stem cells were used to reconstitute irradiated Mls-1^aIE⁺ recipients. These results suggest that clonal deletion of the host- and donor-reactive T cells in both the host- and donor-derived thymocytes is an important mechanism for the induction of transplantation tolerance in allogeneic BM chimeras and that BM-derived APC may be essential for the intrathymic elimination of both the host- and donor-reactive T cells in the BM chimeras.