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 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.


CONCLUSIONS
Arthritic lesions may be induced in Fas-expressing recipients by persistent engrafted syngeneic lymphocytes overexpressing FasL.
Bonardelle
D
D
INSERM U 267; Department of Pathology, H pital Paul-Brousse, Villejuif, France.
Bobé
P
P
Reynès
M
M
Amouroux
J
J
Tricottet
V
V
Godeau
F
F
Kiger
N
N
D000818:Animals; D000843:Ankle Joint / Q000473:pathology; D017209:Apoptosis / Q000276:immunology; D001172:Arthritis, Rheumatoid / Q000276:immunology* / Q000473:pathology; D003601:Cytotoxicity Tests, Immunologic; D053222:Fas Ligand Protein; D006086:Graft vs Host Disease / Q000276:immunology*; D022781:Hepatocytes / Q000276:immunology / Q000473:pathology; D008099:Liver / Q000166:cytology / Q000276:immunology; D008562:Membrane Glycoproteins / Q000276:immunology*; D051379:Mice; D019463:Mice, Inbred MRL lpr; D010522:Periostitis / Q000276:immunology / Q000473:pathology; D013154:Spleen / Q000166:cytology / Q000276:immunology / Q000637:transplantation; D013601:T-Lymphocytes / Q000276:immunology / Q000637:transplantation; D018183:Transplantation Chimera / Q000276:immunology*
D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D008562:Membrane Glycoproteins