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In this study, we identified lymphocytes with cytotoxic potential that may also mediate this feature of synovial pathology.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The cytotoxic potential of lymphocytes and their T cell receptor (TCR) V<jats:sub>\u03b2<\/jats:sub> gene usage were determined using samples of peripheral blood mononuclear cells (PBMCs) and synovial fluid mononuclear cells (SFMCs) from patients with antibiotic\u2010responsive or post\u2010antibiotic LA. Cell phenotypes were analyzed using flow cytometry and intracellular cytokine staining. Immunohistochemistry was performed on post\u2010antibiotic synovial tissue samples.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In SFMC and PBMC samples, the percentages of CD8+ T cells and double\u2010negative T cells (primarily \u03b3\u03b4 T cells) were greater among 22 patients with post\u2010antibiotic LA than in 14 patients with antibiotic\u2010responsive LA. Moreover, CD8+ T cells and \u03b3\u03b4 T cells often expressed cytotoxic mediators, granzyme A\/granzyme B, and perforin. The same 3 TCR V<jats:sub>\u03b2<\/jats:sub> segments were over\u2010represented in both CD4+ T cells and CD8+ T cells in SFMC samples from post\u2010antibiotic LA patients. In synovial tissue samples from 3 patients with post\u2010antibiotic LA, CD8+ T cells intermixed with CD4+ T cells were seen around blood vessels, and 2 patients with microvascular damage had autoantibodies to vascular\u2010associated antigens. One of these 2 patients, the one in whom cytotoxicity appeared to be active, had complement (C5b\u20139) deposition on obliterated vessels. Very few natural killer cells or \u03b3\u03b4 T cells were seen.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>We propose that CD8+ T cell\u2013mediated cytotoxicity, CD4+ T cell help, autoantibodies to vascular antigens, and complement deposition may each have a role in microvasculature damage in post\u2010antibiotic LA.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.42408","type":"journal-article","created":{"date-parts":[[2022,11,22]],"date-time":"2022-11-22T10:44:13Z","timestamp":1669113853000},"page":"782-793","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["<scp>Cell\u2010Mediated<\/scp> Cytotoxicity in Lyme Arthritis"],"prefix":"10.1002","volume":"75","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0738-8653","authenticated-orcid":false,"given":"David","family":"Ord\u00f3\u00f1ez","sequence":"first","affiliation":[{"name":"Massachusetts General Hospital and Harvard Medical School  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