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Inflammatory Arthropathy in MRL Hematopoietic Chimeras Undergoing Fas Mediated Graft-versus-Host Syndrome
DANIELLE BONARDELLE, PIERRE BOBÉ, MICHEL REYNÈS, JACQUES AMOUROUX, VIVIANE TRICOTTET, FRANÇOIS GODEAU, and NICOLE KIGER
ABSTRACT. Objective. To determine whether overexpression of the Fas ligand (FasL) on activated lpr T lymphocytes could induce arthritic lesions when grafted into syngeneic wild-type MRL mice expressing normal Fas receptor levels. Methods. Lethally irradiated MRL+/+ mice were reconstituted with congenic MRL/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 chimeras were histologically examined. Results. The lpr lymphocytes repopulating the spleen overexpressed FasL and had in vitro Fas-mediated cytotoxic activity. Simultaneously, in vivo, articular (synovitis, pannus) and periarticular (periostitis) inflammation with bone resorption were observed. Conclusion. Arthritic lesions may be induced in Fas-expressing recipients by persistent engrafted syngeneic lymphocytes overexpressing FasL. (J Rheumatol 2001;28:956-61) Key Indexing Terms:
FAS LIGAND |