Inflammatory arthropathy in MRL hematopoietic chimeras undergoing Fas mediated graft-versus-host syndrome

Objective. To determine whether overexpression of the Fas ligand (FasL) on activated lpr T lymphocytes could induct arthritic lesions when grafted int o syngeneic wild-type MRL mice expressing normal Fas receptor levels. Methods. Lethally irradiated MRL+/+ mice were reconstituted with congenic M RL/lpr bone marrow cells and splenocytes overexpressing FasL. Fas-mediated cytotoxic properties of repopulating lpr splenic lymphocytes were evaluated in vitro. Simultaneously, the hind paw ankles of the hematopoietic chimera s were histologically examined. Results. The lpr lymphocytes repopulating the spleen overexpressed FasL and had in vitro Fas-mediated cytotoxic activity. Simultaneously. in Live, art icular (synovitis. pannus) and periarticular (periostitis) inflammation wit h bone resorption were observed. Conclusion. Arthritic lesions may be induced in Fas-expressing recipients b y persistent engrafted syngeneic lymphocytes overexpressing FasL.