BONE-MARROW-DERIVED CHIMERISM IN NONIRRADIATED, CYCLOSPORINE-TREATED RATS RECEIVING MICROVASCULARIZED LIMB TRANSPLANTS - EVIDENCE FOR DONOR-DERIVED DENDRITIC CELLS IN RECIPIENT LYMPHOID-TISSUES

Tolerance to donor transplantation antigens develops when recipients a re made chimeric with donor bone marrow. To establish chimerism, the h aemopoietic system of recipients typically is severely compromised. We report on a system in which chimerism develops without ablative thera pies. Immunosuppression with cyclosporin A allowed the lower limb of a rat to be replaced by a microvascularized transplant from a fully all ogeneic donor. Many donor-derived cells populated recipient lymph node s and spleen, and most had the large size, irregular shape and strong major histocompatibility complex (MHC) class II expression that typify dendritic cells. Donor cells were not found in the macrophage-rich re gions of lymphoid tissues, but instead occupied splenic white pulp and lymph node cortex. The donor cells were derived from radiosensitive m arrow precursors, as chimerism was abolished if the grafted limb was i rradiated, or if muscle and skin flaps devoid of bone were grafted. Do nor cells were rare or not detectable in blood, thymus and liver. Wher eas lymphoid chimerism was prominent following limb transfer, donor ce lls were not detected 1-2 weeks after an injection of two femur equiva lents of a marrow suspension. We suggest that dendritic cells that und ergo rapid turnover in lymphoid organs are replaced from allogeneic pr ecursors in bone grafts. The combination of cyclosporin and vasculariz ed bone provides a means for inducing chimerism in lymphoid tissues of non-irradiated recipients.