Lymphadenectomy prior to rat hind limb allotransplantation prevents graft-versus-host disease in chimeric hosts

In previous rat studies, the use of mixed allogeneic chimerism (MAC) to induce host tolerance to hind limb allografts has resulted in severe graft-versus-host disease (GVHD). The purpose of this study was to determine if immunocompetent cells in bone marrow (BM) and/or lymph nodes (LNs) of transplanted limbs were responsible for inducing GVHD in mixed chimeric hosts. [ACIWistar Furth] chimeric rats received ACI hind limbs that were non-irradiated, irradiated (1050 cGy) or lymphadenectomized. Rejection, GVHD and donor chimerism was assessed. Chimeric hosts rejected none of their limbs. However, hosts of non-irradiated hind limbs succumbed to GVHD 22.4±0.8 days after transplantation. In contrast, chimeras that received irradiated or lymphadenectomized ACI hind limbs showed no clinical or histological signs of GVHD at 5 months. We conclude that mixed chimeric hosts are susceptible to GVHD due to the immunocompetent cell load provided by the LNs, not the BM, of hind limb allografts.Abbreviations BM Bone marrow - CPM Counts per minute - CTA Composite tissue allograft - FACS Fluorescence activated cell sorter - FITC Fluorescent iso-thiocyanate - GVH Graft-versus-host - GVHD Graft-versus-host disease - HVG Host-versus-graft - LN Lymph node - MAC Mixed allogeneic chimerism - MHC Major histocompatibility complex - MLR Mixed lymphocyte reaction - MoAb Monoclonal antibody - PBL Peripheral blood lymphocytes - SEM Standard error of mean - TBI Total body irradiation - TCD T-cell depletion/T-cell depleted - TCR T-cell receptor