Single-cell clonal tracing of glandular and circulating T cells identifies a population of CD9+CD8+T cells in primary Sjogren's syndrome

Primary Sjogren's syndrome (pSS) is a complex chronic autoimmune disease in which local tissue damage in exocrine glands is combined with broader systemic involvement across the body in tissues including the skin. These combined manifestations negatively impact patient health and quality of life. While studies have previously reported differences in immune cell composition in the peripheral blood of pSS patients relative to healthy control subjects, a detailed immune cell landscape of the damaged exocrine glands of these patients remains lacking. Through single-cell transcriptomics and repertoire sequencing of immune cells in paired peripheral blood samples and salivary gland biopsies, we present here a preliminary picture of adaptive immune response in pSS. We characterize a number of points of divergence between circulating and glandular immune responses that have been hitherto underappreciated, and identify a novel population of CD8+ CD9+ cells with tissue-residential properties that are highly enriched in the salivary glands of pSS patients. Through comparative analyses with other sequencing data, we also observe a potential connection between these cells and the tissue-resident memory cells found in cutaneous vasculitis lesions. Together, these results indicate a potential role for CD8+ CD9+ cells in mediating glandular and systemic effects associated with pSS and other autoimmune disorders. Primary Sjogren's syndrome (pSS) is a complex, chronic autoimmune disease involving damage to secretory glands and broader systemic manifestations. Though efforts have been made to systematically profile circulating immune cells in pSS patients, the immune landscape within the inflamed glands has remained murky. Through integrated single-cell profiling of circulating and glandular immune cells, we identify a population of CD8+ CD9+ tissue-resident memory T cells uniquely found in the salivary glands in both human patients and animal models. These TRMs express significant levels of chemokines, and their presence is positively correlated with clinical disease activity. Via comparative analyses, we find that these tissue-resident memory T cells may also be potentially observed in the skin, suggesting a possible connection with dermal manifestations of pSS.