The T cell in Sjogren's syndrome: force majeure, not spectateur.
Sjogren's syndrome (SS) is characterized by infiltration of exocrine glands with T and B lymphocytes, leading to glandular dysfunction and frequently accompanied by hypergammaglobulinemia and autoantibodies. The role of T cells, which predominate in the lesions, has attracted much interest. CD4 T cells seem to be responding to autoantigens on apoptotic cells, such as the Ro and La antigens, or to the cytoskeletal antigen α-fodrin. Physical injury to ocular surfaces may also lead to T cell mediated responses to self antigens and perpetuate disease. Within the salivary glands, T cell responsiveness is further promoted by the special capacity of salivary epithelial tissue to provide costimulation and enhanced antigen presentation. Cytokines are key mediators of the T cell contribution to pathology, with roles attributed both to Th1 and Th2 cells. Recently, striking data implicate Th17 cells in the stimulation of B cells, and a role for the related cytokine IL-21 produced by follicular T helper cells is now appreciated. Dysfunction of T regulatory cells has been shown to have a role in the exuberant production of cytokines by Th17 cells. Beyond their role in provoking B cell hyperactivity and immunoglobulin secretion, T cells are directly involved in destruction of glands through Fas and perforin-mediated cytotoxicity. Animal models of SS have confirmed the role of T cell derived cytokines in disease and support a role for effector-memory cells in pathogenesis. Further elucidation of the role of T cells will open avenues for better treatment of SS, whose current management is still mainly supportive.
Temple University School of Medicine, Section of Rheumatology, 3322 North Broad Street, Suite 205, Philadelphia, PA 19140, USA.
Namrata
N
Singh
Philip L
PL
Cohen
D000818:Animals; D017209:Apoptosis / Q000276:immunology; D001323:Autoantibodies / Q000096:biosynthesis / Q000276:immunology*; D001324:Autoantigens / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D002450:Cell Communication / Q000276:immunology; D006801:Humans; D007378:Interleukins / Q000096:biosynthesis / Q000276:immunology; D008213:Lymphocyte Activation; D051379:Mice; D054353:Perforin / Q000235:genetics / Q000276:immunology; D012469:Salivary Glands / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D012859:Sjogren's Syndrome / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D019014:fas Receptor / Q000235:genetics / Q000276:immunology; D000098546:Interleukin-21
D001323:Autoantibodies; D001324:Autoantigens; C491901:FAS protein, human; D007378:Interleukins; D019014:fas Receptor; D054353:Perforin; D000098546:Interleukin-21