THYMUS TRANSPLANTATION, A CRITICAL FACTOR FOR CORRECTION OF AUTOIMMUNE-DISEASE IN AGING MRL + MICE/

MRL/MP-+/+ (MRL/+) mice develop pancreatitis and sialoadenitis after t hey reach 7 months of age. Conventional bone marrow transplantation ha s been found to be ineffective in the treatment of these forms of appa rent autoimmune disease. Old MRL/+ mice show a dramatic thymic involut ion with age. Hematolymphoid reconstitution is incomplete when fetal l iver cells (as a source of hemopoietic stem cells) plus fetal bone (FB ; which is used to recruit stromal cells) are transplanted from immuno logically normal C57BL/6 donor mice to MRL/+ female recipients. Embryo nic thymus from allogeneic C57BL/6 donors was therefore engrafted alon g with either bone marrow or fetal hematopoietic cells (FHCs) plus fra gments of adult or fetal bone. More than seventy percent of old MRL/mice (>7 months) that had been given a fetal thymus (FT) transplant pl us either bone marrow or FHCs and also bone fragments survived more th an 100 days after treatment. The mice that received FHCs, FB, plus FT from allogeneic donors developed normal T cell and B cell functions. S erum amylase levels decreased in these mice whereas they increased in the mice that received FHCs and FB but not FT. The pancreatitis and si aloadenitis already present at the time of transplantations were fully corrected according to histological analysis by transplants of alloge neic FHCs, FB and FT in the MRL/+ mice. These findings are taken as an experimental indication that perhaps stem cell transplants along with FT grafts might represent a useful strategy for treatment of autoimmu ne diseases in aged humans.