{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T18:09:24Z","timestamp":1791828564119,"version":"4.3.4"},"reference-count":69,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2019,8,10]],"date-time":"2019-08-10T00:00:00Z","timestamp":1565395200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Fondo de Investigaci\u00f3n de la Seguridad Social, Instituto de Salud Carlos III","award":["PI18\/01726"],"award-info":[{"award-number":["PI18\/01726"]}]},{"name":"Actividades de I+D de la Comunidad de Madrid en Biomedicina","award":["B2017\/BMD-3804"],"award-info":[{"award-number":["B2017\/BMD-3804"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Patients with long-term, treated, rheumatoid arthritis (RA) show abnormalities in their circulating CD4+ T-lymphocytes, but whether this occurs in recently diagnosed na\u00efve patients to disease-modifying drugs (DMARDs) is under discussion. These patients show heterogeneous clinical response to methotrexate (MTX) treatment. We have examined the count of circulating CD4+ T-lymphocytes, and their na\u00efve (TN), central memory (TCM), effector memory (TEM) and effector (TE) subsets, CD28 expression and V\u03b2 TCR repertoire distribution by polychromatic flow cytometry in a population of 68 DMARD-na\u00efve recently diagnosed RA patients, before and after 3 and 6 months of MTX treatment. At pre-treatment baseline, patients showed an expansion of the counts of CD4+ TN, TEM, TE and TCM lymphocyte subsets, and of total CD4+CD28\u2212 cells and of the TE subset with a different pattern of numbers in MTX responder and non-responders. The expansion of CD4+TEM lymphocytes showed a predictive value of MTX non-response. MTX treatment was associated to different modifications in the counts of the CD4+ subsets and of the V\u03b2 TCR repertoire family distribution and in the level of CD28 expression in responders and non-responders. In conclusion, the disturbance of CD4+ lymphocytes is already found in DMARD-na\u00efve RA patients with different patterns of alterations in MTX responders and non-responders.<\/jats:p>","DOI":"10.3390\/cells8080871","type":"journal-article","created":{"date-parts":[[2019,8,12]],"date-time":"2019-08-12T06:38:02Z","timestamp":1565591882000},"page":"871","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["The Abnormal CD4+T Lymphocyte Subset Distribution and Vbeta Repertoire in New-onset Rheumatoid Arthritis Can Be Modulated by Methotrexate Treament"],"prefix":"10.3390","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1775-4645","authenticated-orcid":false,"given":"Jorge","family":"Monserrat","sequence":"first","affiliation":[{"name":"Laboratory of Immune System Diseases, University of Alcal\u00e1, Alcal\u00e1 de Henares, 28871 Madrid, Spain"},{"name":"Department of Medicine, University Hospital \u201cPr\u00edncipe de Asturias\u201d, University of Alcal\u00e1 and Instituto Ram\u00f3n y Cajal de Investigaci\u00f3n Sanitaria (IRYCIS), Alcal\u00e1 de Henares, 28871 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina","family":"Boh\u00f3rquez","sequence":"additional","affiliation":[{"name":"Department of Medicine, University Hospital \u201cPr\u00edncipe de Asturias\u201d, University of Alcal\u00e1 and Instituto Ram\u00f3n y Cajal de Investigaci\u00f3n Sanitaria (IRYCIS), Alcal\u00e1 de Henares, 28871 Madrid, Spain"},{"name":"Immune System Diseases-Rheumatology Service, University Hospital \u201cPr\u00edncipe de Asturias\u201d, Alcal\u00e1 de Henares, 28871 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana Mar\u00eda","family":"G\u00f3mez Lahoz","sequence":"additional","affiliation":[{"name":"Laboratory of Immune System Diseases, University of Alcal\u00e1, Alcal\u00e1 de Henares, 28871 Madrid, Spain"},{"name":"Immune System Diseases-Rheumatology Service, University Hospital \u201cPr\u00edncipe de Asturias\u201d, Alcal\u00e1 de Henares, 28871 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Atusa","family":"Movasat","sequence":"additional","affiliation":[{"name":"Department of Medicine, University Hospital \u201cPr\u00edncipe de Asturias\u201d, University of Alcal\u00e1 and Instituto Ram\u00f3n y Cajal de Investigaci\u00f3n Sanitaria (IRYCIS), Alcal\u00e1 de Henares, 28871 Madrid, Spain"},{"name":"Immune System Diseases-Rheumatology Service, University Hospital \u201cPr\u00edncipe de Asturias\u201d, Alcal\u00e1 de Henares, 28871 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana","family":"P\u00e9rez","sequence":"additional","affiliation":[{"name":"Department of Medicine, University Hospital \u201cPr\u00edncipe de Asturias\u201d, University of Alcal\u00e1 and Instituto Ram\u00f3n y Cajal de Investigaci\u00f3n Sanitaria (IRYCIS), Alcal\u00e1 de Henares, 28871 Madrid, Spain"},{"name":"Immune System Diseases-Rheumatology Service, University Hospital \u201cPr\u00edncipe de Asturias\u201d, Alcal\u00e1 de Henares, 28871 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luc\u00eda","family":"Ru\u00edz","sequence":"additional","affiliation":[{"name":"Department of Medicine, University Hospital \u201cPr\u00edncipe de Asturias\u201d, University of Alcal\u00e1 and Instituto Ram\u00f3n y Cajal de Investigaci\u00f3n Sanitaria (IRYCIS), Alcal\u00e1 de Henares, 28871 Madrid, Spain"},{"name":"Immune System Diseases-Rheumatology Service, University Hospital \u201cPr\u00edncipe de Asturias\u201d, Alcal\u00e1 de Henares, 28871 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"D\u00edaz","sequence":"additional","affiliation":[{"name":"Laboratory of Immune System Diseases, University of Alcal\u00e1, Alcal\u00e1 de Henares, 28871 Madrid, Spain"},{"name":"Immune System Diseases-Rheumatology Service, University Hospital \u201cPr\u00edncipe de Asturias\u201d, Alcal\u00e1 de Henares, 28871 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luis","family":"Chara","sequence":"additional","affiliation":[{"name":"Laboratory of Immune System Diseases, University of Alcal\u00e1, Alcal\u00e1 de Henares, 28871 Madrid, Spain"},{"name":"Immune System Diseases-Rheumatology Service, University Hospital \u201cPr\u00edncipe de Asturias\u201d, Alcal\u00e1 de Henares, 28871 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana Isabel","family":"S\u00e1nchez","sequence":"additional","affiliation":[{"name":"Department of Medicine, University Hospital \u201cPr\u00edncipe de Asturias\u201d, University of Alcal\u00e1 and Instituto Ram\u00f3n y Cajal de Investigaci\u00f3n Sanitaria (IRYCIS), Alcal\u00e1 de Henares, 28871 Madrid, Spain"},{"name":"Immune System Diseases-Rheumatology Service, University Hospital \u201cPr\u00edncipe de Asturias\u201d, Alcal\u00e1 de Henares, 28871 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fernando","family":"Albarr\u00e1n","sequence":"additional","affiliation":[{"name":"Department of Medicine, University Hospital \u201cPr\u00edncipe de Asturias\u201d, University of Alcal\u00e1 and Instituto Ram\u00f3n y Cajal de Investigaci\u00f3n Sanitaria (IRYCIS), Alcal\u00e1 de Henares, 28871 Madrid, Spain"},{"name":"Immune System Diseases-Rheumatology Service, University Hospital \u201cPr\u00edncipe de Asturias\u201d, Alcal\u00e1 de Henares, 28871 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ignacio","family":"Sanz","sequence":"additional","affiliation":[{"name":"Division of Immunology and Rheumatology, Department of Medicine, Emory University, Atlanta, GA 30322, 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