Systemic lupus erythematosus is characterized by autoantibodies against nuclear antigens. In this issue of Immunity, Al Souz et al. report that kidney damage in lupus nephritis is sustained by stem-like CD8+ T cells that migrate from lymphoid tissues and then, driven by CD4+ T cells and IL-15 and IL-21, differentiate into cytotoxic effectors within tissue and retain pathogenic function despite exhaustion markers.
