Where do T cells stand in rheumatoid arthritis?
Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by destruction of cartilage and bone. The destructive lesions result from both immune responses and non-antigen-specific inflammatory processes. Little is known about the primary cause of RA. Although the primacy of T-cell-related events early in the disease remains debated, strong evidence indicates that autoantigen recognition by specific T cells is crucial to the pathophysiology of rheumatoid synovitis. We will discuss evolving concepts about T-cell involvement in RA and the roles for various T cell subsets in the development of joint abnormalities. The hypothesis that RA is a T-cell driven disease was put forward when studies of RA synovium showed numerous T cells carrying activation markers. These T cells were found to participate in the complex network of cell- and mediator-driven events leading to joint destruction. Conceivably, these T cells may be stimulated by an autoantigen (whether specific to the joints or ubiquitous), a highly conserved foreign protein cross-reacting with its human homolog, or a neo-antigen expressed as a result of posttranslational events. For many years, animal models have provided valuable evidence supporting a role for T cells in RA. We will review three murine models of arthritis caused by different mechanisms. In collagen-induced arthritis, the immune response to a joint antigen is mediated by pathogenic Th1 cells that elicit severe inflammatory synovitis. Spontaneous arthritis in K/BxN T-cell-receptor transgenic mice is related to an adaptive immune response against a ubiquitous protein whose end-stage effector mechanisms are heavily dependent on the innate immune system. In the SKG model of autoimmune inflammatory arthritis, a point mutation in the gene encoding a key signal-transduction molecule in T cells causes defective T cell selection in the thymus, which releases polyclonal autoreactive T cells. Studies in these and other animal models have established that a variety of T-cell subsets whose roles vary with cell location and disease stage can contribute to synovitis. Finally, in addition to direct autoimmune attack by effector T cells, arthritis may result from defective homeostatic control of immunity by regulatory T cells.
Fournier
Catherine
C
Cochin Institute (Inserm U567, CNRS UMR8104, René Descartes University) Immunology Department, Hardy A Pavillion, 27, rue du Faubourg Saint-Jacques, 75674 Paris cedex 14, France. fournier@cochin.inserm.fr
D000818:Animals; D001172:Arthritis, Rheumatoid / Q000276:immunology*; D015551:Autoimmunity; D003094:Collagen / Q000502:physiology; D004195:Disease Models, Animal; D017261:Glycosylphosphatidylinositols / Q000276:immunology; D006801:Humans; D007150:Immunohistochemistry; D008565:Membrane Proteins / Q000276:immunology; D051379:Mice; D017354:Point Mutation; D013583:Synovial Membrane / Q000166:cytology / Q000503:physiopathology; D013585:Synovitis / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology
D017261:Glycosylphosphatidylinositols; D008565:Membrane Proteins; C484452:Pigq protein, mouse; D003094:Collagen