GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE318nnn/GSE318514/primaryOK200GenomicsMus musculusGenome binding/occupancy profiling by high throughput sequencing Expression profiling by high throughput sequencing Otherhttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE318514GEOGSEfalseOrgan injury in systemic autoimmunity is mediated by stem-like CD8 T cells arising from tissue-draining lymph nodesChronic antigen exposure in cancer and infection generates hypofunctional, stem-like CD8 T cells that replenish tissue effector cells for tumor or pathogen control. CD8 T cells infiltrate kidneys in systemic lupus erythematosus, but their origin, differentiation, and function remain incompletely understood. We identified in lupus-prone mice TCF1⁺ stem-like CD8 T cells in renal-draining lymph nodes that underwent TCR-dependent, antigen-driven expansion with differentiation into cytotoxic kidney-infiltrating cells that promoted tissue injury contingent on CD4 T cell help and IL-21/IL-15 signaling. CD8 T cell differentiation was marked by persistent AP-1 activity and cytotoxic function despite immune checkpoint upregulation. We found a parallel program of CD8 T cell differentiation in kidneys of patients with lupus nephritis, reflecting shared pathogenesis. This T cell differentiation program is analogous to that in chronic infections and cancer, indicating conservation across states of chronic antigen stimulation; however, CD8 T cells in systemic autoimmunity retain effector function despite terminal differentiation.2026/04/20GSE318514GSM9496926GSM9496948GSM9496949GSM9496905GSM9496927GSM9496906GSM9496928GSM9496929GSM9496907GSM9496944GSM9496922GSM9496923GSM9496945GSM9496946GSM9496924GSM9496925GSM9496947GSM9496908GSM9496909GSM9496930GSM9496931GSM9496932GSM9496910GSM9496915GSM9496937GSM9496916GSM9496938GSM9496917GSM9496939GSM9496918GSM9496911GSM9496933GSM9496912GSM9496934GSM9496935GSM9496913GSM9496914GSM9496936GSM9496919GSM9496940GSM9496941GSM9496920GSM9496942GSM9496943GSM949692124247318514Mus musculus[42013863]