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The production of IFN\u03b3 by T cells was evaluated at baseline and after 1, 2, 4, and 8 years of anti-TNF agents by means of a QuantiFERON-TB Gold In-Tube assay. The T cell proliferation and surface co-expression of CD25\/CD134 in response to phytohaemagglutinin together with the <jats:italic>in vitro<\/jats:italic> impact of anti-TNF therapy on the functional capacity of T cells were evaluated after 8 years from the onset of the biological treatment. Age-matched healthy donors were enrolled as controls. The quantitative mitogen-induced IFN\u03b3 responses significantly increased with respect to baseline at each time point, apart from the determination after 4 years. We found an increased expression of CD25\/CD134 in CD4<jats:sup>+<\/jats:sup> compared to CD8<jats:sup>+<\/jats:sup> T cells both in patients and controls. The <jats:italic>in vitro<\/jats:italic> addition of anti-TNF agents induced a significant decrease of both the IFN\u03b3 response and of CD25\/CD134, whereas no effect on the intensity of the proliferative response was observed. Our data provide a biological basis for the reassuring issues on the safety of long-term anti-TNF treatment in patients with IMID.<\/jats:p>","DOI":"10.1038\/s41598-018-26097-x","type":"journal-article","created":{"date-parts":[[2018,5,14]],"date-time":"2018-05-14T15:27:12Z","timestamp":1526311632000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Changes in T cell effector functions over an 8-year period with TNF antagonists in patients with chronic inflammatory rheumatic diseases"],"prefix":"10.1038","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0060-0749","authenticated-orcid":false,"given":"Ilaria","family":"Sauzullo","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rossana","family":"Scrivo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paola","family":"Sessa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fabio","family":"Mengoni","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vincenzo","family":"Vullo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guido","family":"Valesini","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1286-467X","authenticated-orcid":false,"given":"Claudio Maria","family":"Mastroianni","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2018,5,18]]},"reference":[{"key":"26097_CR1","doi-asserted-by":"publisher","first-page":"244","DOI":"10.1016\/S0140-6736(89)90430-3","volume":"2","author":"FM Brennan","year":"1989","unstructured":"Brennan, F. 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