Rheumatoid synovial fluid T cells are sensitive to APO2L/TRAIL.
The infiltration and accumulation of T cells in the rheumatoid arthritis (RA) synovial fluid (SF) are hallmarks of disease. We aimed to assess the functional relevance of FasL and of APO2L/TRAIL in the persistence of T cells in the rheumatoid SF. We have analyzed the expression of the activation markers HLA-DR and CD69 and also of the death receptor Fas/CD95 and death ligands FasL or APO2L/TRAIL in CD3+ lymphocytes from SF of 62 RA patients, together with their sensitivity to anti-Fas mAb or to rAPO2L/TRAIL, using as controls T lymphocytes present in SF of 20 patients with traumatic arthritis. T lymphocytes infiltrated in SF of RA patients have a chronically activated phenotype, but they are resistant to Fas-induced toxicity. However, they are more susceptible to rAPO2L/TRAIL than T cells in the SF of traumatic arthritis patients. In addition, we found very low amounts of bioactive FasL and APO2L/TRAIL associated with exosomes in SF from RA patients as compared with SF from traumatic arthritis patients. The observation on the sensitivity of RA SF T cells to rAPO2L could have therapeutic implications because bioactive APO2L/TRAIL could be beneficial as a RA treatment.
Martínez-Lorenzo
María José
MJ
Instituto Aragonés de Ciencias de la Salud and Servicio de Inmunología, Hospital Clínico Universitario Lozano Blesa. Zaragoza, Spain. linm@hcu-lblesa.es
Anel
Alberto
A
Saez-Gutierrez
Berta
B
Royo-Cañas
María
M
Bosque
Alberto
A
Alava
María Angeles
MA
Piñeiro
Andrés
A
Lasierra
Pilar
P
Asín-Ungría
Jaime
J
Larrad
Luis
L
D015703:Antigens, CD / Q000276:immunology / Q000378:metabolism; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology / Q000378:metabolism; D001172:Arthritis, Rheumatoid / Q000276:immunology*; D017252:CD3 Complex / Q000276:immunology / Q000378:metabolism; D002478:Cells, Cultured; D053222:Fas Ligand Protein / Q000037:antagonists & inhibitors / Q000276:immunology / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D006684:HLA-DR Antigens / Q000276:immunology / Q000378:metabolism; D006801:Humans; D019169:Jurkat Cells; D037181:Lectins, C-Type; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D013582:Synovial Fluid / Q000166:cytology* / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000037:antagonists & inhibitors / Q000276:immunology* / Q000378:metabolism; D019014:fas Receptor / Q000276:immunology / Q000378:metabolism; D000099192:CD69 Antigens
D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D017252:CD3 Complex; D053222:Fas Ligand Protein; D006684:HLA-DR Antigens; D037181:Lectins, C-Type; D053221:TNF-Related Apoptosis-Inducing Ligand; D019014:fas Receptor; D000099192:CD69 Antigens