Arthritis: where are the T cells?

In a paper in the previous issue of Arthritis Research and Therapy Angyal and colleagues [1] ask the fundamental question of how and where T cells contribute to arthritis pathogenesis. Th at T cells do contribute to arthritis pathogenesis is widely accepted: HLA-DRB1 is the best-established genetic locus influencing rheumatoid arthritis (RA); and other genetic risk factors, including PTPN22, are also relevant for T-cell function [2]. Abatacept, which blocks T-helper (Th) cell co-stimulation, is an effective treatment for RA patients [3]. Nonetheless, the specificity of pathogenic T cells in RA remains unknown. Increasing evidence suggests that recognition of systemically expressed antigens by T cells can induce arthritis. Systemic autoimmune responses towards glucose-6-phosphate isomerase [4,5], fibrinogen [6], or transgenically expressed hemagglutinin [7] induce arthritis in mice. Moreover, systemic alterations that impact on T-cell reactivity result in arthritis. The so-called SKG mice and gp130 mutant mice spontaneously develop chronic joint inflammation [8]. In both models particular arthritogenic autoantigens have not been identified. Instead, T cell receptor signaling is altered in SKG mice, resulting in a broad repertoire of low-affinity autoreactive T cells. Autoimmunity towards systemically expressed antigens might well be relevant in human arthritis. Adaptive immune responses to citrullinated peptides are a hallmark of RA and the origin of the recognized citrullinated peptides is not restricted to joint-specific antigens [2]. Taken together, mounting evidence puts into question the notion that arthritogenic antigens must be joint-specific.It is against this background that Angyal and colleagues [1] asked where the pathogenic T cells in arthritis exert effector functions. After immunizing with proteoglycan, they obtained spleen cells from arthritic mice, labeled the T cells with a fluorescent dye, and transferred the labeled T cells together with the antige