{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T18:20:47Z","timestamp":1788373247962,"version":"build-2803163510"},"reference-count":76,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,3,30]],"date-time":"2023-03-30T00:00:00Z","timestamp":1680134400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>Inclusion body myositis (IBM) is a progressive inflammatory myopathy characterised by skeletal muscle infiltration and myofibre invasion by CD8<jats:sup>+<\/jats:sup> T lymphocytes. In some cases, IBM has been reported to be associated with a systemic lymphoproliferative disorder of CD8<jats:sup>+<\/jats:sup> T cells exhibiting a highly differentiated effector phenotype known as T cell Large Granular Lymphocytic Leukemia (T-LGLL). <\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We investigated the incidence of a CD8<jats:sup>+<\/jats:sup> T-LGL lymphoproliferative disorder in 85 IBM patients and an aged-matched group of 56 Healthy Controls (HC). Further, we analysed the phenotypical characteristics of the expanded T-LGLs and investigated whether their occurrence was associated with any particular HLA alleles or clinical characteristics. <\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Blood cell analysis by flow cytometry revealed expansion of T-LGLs in 34 of the 85 (40%) IBM patients. The T cell immunophenotype of T-LGL<jats:sub>HIGH<\/jats:sub> patients was characterised by increased expression of surface molecules including CD57 and KLRG1, and to a lesser extent of CD94 and CD56 predominantly in CD8<jats:sup>+<\/jats:sup> T cells, although we also observed modest changes in CD4<jats:sup>+<\/jats:sup> T cells and \u03b3\u03b4 T cells. Analysis of Ki67 in CD57<jats:sup>+<\/jats:sup> KLRG1<jats:sup>+<\/jats:sup> T cells revealed that only a small proportion of these cells was proliferating. Comparative analysis of CD8<jats:sup>+<\/jats:sup> and CD4<jats:sup>+<\/jats:sup> T cells isolated from matched blood and muscle samples donated by three patients indicated a consistent pattern of more pronounced alterations in muscles, although not significant due to small sample size. In the T-LGL<jats:sub>HIGH<\/jats:sub> patient group, we found increased frequencies of perforin-producing CD8<jats:sup>+<\/jats:sup> and CD4<jats:sup>+<\/jats:sup> T cells that were moderately correlated to combined CD57 and KLRG1 expression. Investigation of the HLA haplotypes of 75 IBM patients identified that carriage of the HLA-C*14:02:01 allele was significantly higher in T-LGL<jats:sub>HIGH<\/jats:sub> compared to T-LGL<jats:sub>LOW<\/jats:sub> individuals. Expansion of T-LGL was not significantly associated with seropositivity patient status for anti-cytosolic 5'-nucleotidase 1A autoantibodies. Clinically, the age at disease onset and disease duration were similar in the T-LGL<jats:sub>HIGH<\/jats:sub> and T-LGL<jats:sub>LOW<\/jats:sub> patient groups. However, metadata analysis of functional alterations indicated that patients with expanded T-LGL more frequently relied on mobility aids than T-LGL<jats:sub>LOW<\/jats:sub> patients indicating greater disease severity. <\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Altogether, these results suggest that T-LGL expansion occurring in IBM patients is correlated with exacerbated immune dysregulation and increased disease burden.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2023.1153789","type":"journal-article","created":{"date-parts":[[2023,3,30]],"date-time":"2023-03-30T10:22:41Z","timestamp":1680171761000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":11,"title":["Uncovering the significance of expanded CD8+ large granular lymphocytes in inclusion body myositis: Insights into T cell phenotype and functional alterations, and disease 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