{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T09:32:41Z","timestamp":1781688761308,"version":"3.54.5"},"reference-count":40,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2025,5,15]],"date-time":"2025-05-15T00:00:00Z","timestamp":1747267200000},"content-version":"vor","delay-in-days":134,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100009053","name":"Wellcome Trust DBT India Alliance","doi-asserted-by":"publisher","award":["IA\/CPHI\/18\/1\/503975"],"award-info":[{"award-number":["IA\/CPHI\/18\/1\/503975"]}],"id":[{"id":"10.13039\/501100009053","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005809","name":"Hyderabad Eye Research Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100005809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clin &amp; Trans Imm"],"published-print":{"date-parts":[[2025,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objectives<\/jats:title><jats:p>Peripheral blood is frequently used to study the immune response in human uveitis because of the inaccessibility of ocular tissue samples. To determine whether peripheral blood immune cells accurately reflect the intraocular immune response, we compared the T\u2010cell profiles and antigen\u2010specific cytokine responses between paired vitreous and peripheral blood samples from patients with sight\u2010threatening posterior uveitis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We collected paired vitreous and peripheral blood mononuclear cells (PBMCs) from 24 patients with posterior uveitis. Multi\u2010parametric flow cytometry was employed to identify surface and intracellular cytokine markers after activation with candidate antigenic peptides [<jats:italic>Mycobacterium tuberculosis<\/jats:italic> (MTb) peptides and retinal autoantigens]. Data were analysed through manual gating, unsupervised clustering and dimensionality reduction (FlowSOM, FlowJo).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The CD8<jats:sup>+<\/jats:sup>\/CD4<jats:sup>+<\/jats:sup> ratio in a representative set of seven paired samples was higher in the vitreous than in PBMCs. Vitreous CD4<jats:sup>+<\/jats:sup> and CD8<jats:sup>+<\/jats:sup> cells displayed greater polyfunctional potential (TNF\u03b1<jats:sup>+<\/jats:sup>IFN\u03b3<jats:sup>+<\/jats:sup>IL\u20102<jats:sup>+<\/jats:sup> and PMA\/ionomycin activation) than PBMCs. Upon antigen\u2010specific activation <jats:italic>in vitro<\/jats:italic>, vitreous CD8<jats:sup>+<\/jats:sup> T\u00a0cells (but not CD4<jats:sup>+<\/jats:sup> T\u00a0cells) showed a stronger polyfunctional response than PBMCs against both MTb (in TB\u2010immunoreactive patients) and retinal autoantigens. Unsupervised clustering identified 15 distinct CD3<jats:sup>+<\/jats:sup> T\u2010cell metaclusters, each with unique profiles in the vitreous and PBMCs. Significant cluster enrichment was observed among the vitreous infiltrating cells in TB\u2010immunoreactive cases compared to non\u2010TB uveitis, but no such enrichment was found among PBMCs in either patient cohort.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The vitreous T\u2010cell compartment in this group of uveitis patients was functionally dominated by antigen\u2010responsive cytotoxic CD8<jats:sup>+<\/jats:sup> T\u00a0cells and was distinct from the corresponding peripheral blood compartment.<\/jats:p><\/jats:sec>","DOI":"10.1002\/cti2.70036","type":"journal-article","created":{"date-parts":[[2025,5,16]],"date-time":"2025-05-16T01:36:36Z","timestamp":1747359396000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Antigen\u2010specific polyfunctional cytotoxic T\u00a0cells differentiate intraocular from peripheral blood immune responses in posterior uveitis"],"prefix":"10.1002","volume":"14","author":[{"given":"Kaiser","family":"Alam","sequence":"first","affiliation":[{"name":"Ocular Immunology Laboratory, Prof Brien Holden Eye Research Centre LV Prasad Eye Institute  Hyderabad India"},{"name":"Multidisciplinary Unit of Research on Translational Initiatives (MURTI) Research Centre, Visvesvaraya Bhavan, Division of Microbiology, Department of Life Sciences, School of Science Gandhi Institute of Technology and Management (GITAM)  Visakhapatnam India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arun","family":"Raina","sequence":"additional","affiliation":[{"name":"Ocular Immunology Laboratory, Prof Brien Holden Eye Research Centre LV Prasad Eye Institute  Hyderabad India"},{"name":"Institute of Genomics and Integrative Biology  New Delhi India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bibhuprasad","family":"Das","sequence":"additional","affiliation":[{"name":"Ocular Immunology Laboratory, 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