T-Cell Dysregulation in Systemic Lupus Erythematosus: Pathophysiology and Opportunities for Biomarker Development

T cells in SLE patients are dysfunctional as a result of altered signalling inputs and altered signal processing. They contribute to pathogenesis through expansion of autoreactive T cells, aberrant B-cell help and direct T cell-mediated tissue damage. Tissue inflammation and damage, in turn, produce nuclear autoantigens and perpetuate antigen presentation to T cells. Improvements in T cell-targeted therapy will require biomarkers of T-cell dysfunction that predict clinical response. Criteria for defining such biomarkers in SLE are discussed here. Phenotypes associated with T-cell activation, specific effector functions, and/or altered proliferative and homeostatic dynamics are promising candidates.