CD8+ T cell heterogeneity and function in lupus nephritis: a focused review
Abstract
Lupus nephritis (LN) is a severe manifestation of systemic lupus erythematosus marked by immune complex deposition and tissue-specific inflammation. Advances in single-cell transcriptomics and high-dimensional immune profiling have revealed that CD8+ T cells form a highly heterogeneous and compartment-dependent landscape across peripheral blood, kidney, and urine. This review aims to delineate how compartment-specific phenotypes and signaling programs of CD8+ T cells collectively shape the immunopathogenesis of lupus nephritis (LN). We synthesize current evidence into a unified blood-kidney-urine circuit model, in which systemic priming of circulating CD8+ T pools is followed by renal recruitment, tissue retention and functional reprogramming of kidney-infiltrating populations, cytotoxic and inflammatory tissue injury, and subsequent release of intrarenal immune signatures into urine. Circulating CD8+ T cells include IFN-I-primed naïve-like, effector-memory, and cytotoxic subsets that contribute to systemic immune activation. Within the kidney, infiltrating CD8+ T cells display pronounced clonal expansion, tissue-resident and exhaustion-associated phenotypes, and metabolic reprogramming, all of which correlate with local inflammation and histopathologic severity. Urine-derived CD8+ T cells, increasingly recognized as a non-invasive proxy for intrarenal immunity, recapitulate key transcriptional programs of kidney-infiltrating populations and provide a dynamic readout of…
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