The 'T paradox' in inflammatory arthritis.

Classic regulatory T (T) cells expressing CD4 and the hallmark transcription factor FOXP3 are integral to the prevention of multi-system autoimmunity. However, immune-mediated arthritis is often associated with increased numbers of T cells in the inflamed joints. To understand these seemingly conflicting observations, which we collectively describe as 'the T paradox', we provide an overview of T cell biology with a focus on T cell heterogeneity, function and dysfunction in arthritis. We discuss how the inflamed environment constrains the immunosuppressive activity of T cells while also promoting the differentiation of T17-like T cell, exT cell (effector T cells that were formerly T cells), and osteoclastogenic T cell subsets that mediate tissue injury. We present a new framework to understand T cells in joint inflammation and define potential strategies for T cell-directed interventions in human inflammatory arthritis.