Role of intrathymic clonal deletion and peripheral anergy in transplantation tolerance induced by bone marrow transplantation in mice conditioned with a nonmyeloablative regimen.

摘要: We have investigated the mechanism of tolerance induced by allogeneic bone marrow transplantation (BMT) in mice conditioned with a nonmyeloablative regimen. Permanent mixed chimerism and skin allograft were achieved when recipient B10 (H-2b) pre-treated anti-CD4 anti-CD8 mAbs, thymic irradiation, 3 Gy whole body followed injection B10.A (H-2a) cells. V beta 11+ T cells are normally deleted I-E+ mice, but not I-E- mice. In spleens B10.A-->B10 chimeras, reduced detectable first 6 wk after BMT, later became undetectable. Splenic unresponsive to receptor cross-linking 11-specific mAb, demonstrating anergy. also detected that thymectomized before BMT. PBL undetectable for at least 1.5 yr. Thymocyte extensive clonal deletion mature thymocytes observed as early 10 days post-BMT all subsequent time points thymi chimeras. Rare donor day thymi, these increased progressively frequency times. chimeras prepared reciprocal strain combination, B10-->B10.A, PBL. Together, our results implicate both central peripheral anergy A very low number intrathymic or density Ag expression is sufficient mediate recognize Ags.