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While conventional \u03b1\u03b2 T cells have been extensively studied, the contribution of \u03b3\u03b4 T cells to RA pathogenesis remains insufficiently understood. Unlike \u03b1\u03b2 T cells, \u03b3\u03b4 T cells recognize antigens independently of major histocompatibility complex (MHC) restriction, and their surface receptor expression plays a pivotal role in regulating effector functions. This study aimed to investigate the phenotype and surface receptor profile of \u03b3\u03b4 T cells in RA patients undergoing anti-TNF therapy, to better understand their potential immunoregulatory and prognostic significance. Peripheral blood samples were collected from RA patients before and during treatment with TNF inhibitors, as well as from healthy controls. Flow cytometry was used to quantify \u03b3\u03b4 T cell frequency and to assess the expression of selected activation, differentiation, and exhaustion markers on their surface. RA patients exhibited a significant reduction in the frequency of circulating \u03b3\u03b4 T cells compared with healthy controls. Moreover, \u03b3\u03b4 T cells in RA displayed phenotypic features of advanced differentiation and functional exhaustion, including altered expression of key surface receptors. The observed alterations in \u03b3\u03b4 T cell phenotype and receptor expression suggest chronic immune activation in RA. These findings highlight the potential of \u03b3\u03b4 T cell surface markers as candidate biomarkers for disease activity and response to anti-TNF therapy.<\/jats:p>","DOI":"10.1007\/s13577-026-01393-1","type":"journal-article","created":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T17:13:17Z","timestamp":1780593197000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Immune imbalance in rheumatoid arthritis: insights from \u03b3\u03b4 T cell receptor phenotyping"],"prefix":"10.1007","volume":"39","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1222-4231","authenticated-orcid":false,"given":"Sylwia","family":"Bia\u0142y","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1048-5254","authenticated-orcid":false,"given":"Joanna","family":"Wieli\u0144ska","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7589-8404","authenticated-orcid":false,"given":"Kinga Maria","family":"Tyczy\u0144ska","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3606-173X","authenticated-orcid":false,"given":"Jerzy","family":"\u015awierkot","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9744-0376","authenticated-orcid":false,"given":"Katarzyna","family":"Bogunia-Kubik","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,6,4]]},"reference":[{"key":"1393_CR1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaut.2019.102400","author":"HU Scherer","year":"2020","unstructured":"Scherer HU, H\u00e4upl T, Burmester GR. 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