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Further, a significant genetic linkage to MHC genes suggests that T lymphocytes play an important role in the pathogenesis of CIDs including juvenile idiopathic arthritis (JIA). However, the functions of T lymphocytes in established disease remain elusive. Here we dissect the transcriptional and the clonal heterogeneity of synovial T lymphocytes in JIA patients by single\u2010cell RNA sequencing combined with T cell receptor profiling on the same cells. We identify clonally expanded subpopulations of T lymphocytes expressing genes reflecting recent activation by antigen\n                    <jats:italic>in situ<\/jats:italic>\n                    . A PD\u20101\n                    <jats:sup>+<\/jats:sup>\n                    <jats:italic>TOX<\/jats:italic>\n                    <jats:sup>+<\/jats:sup>\n                    <jats:italic>EOMES<\/jats:italic>\n                    <jats:sup>+<\/jats:sup>\n                    population of CD4\n                    <jats:sup>+<\/jats:sup>\n                    T lymphocytes expressed immune regulatory genes and chemoattractant genes for myeloid cells. A PD\u20101\n                    <jats:sup>+<\/jats:sup>\n                    <jats:italic>TOX<\/jats:italic>\n                    <jats:sup>+<\/jats:sup>\n                    <jats:italic>BHLHE40<\/jats:italic>\n                    <jats:sup>+<\/jats:sup>\n                    population of CD4\n                    <jats:sup>+<\/jats:sup>\n                    , and a mirror population of CD8\n                    <jats:sup>+<\/jats:sup>\n                    T lymphocytes expressed genes driving inflammation, and genes supporting B lymphocyte activation\n                    <jats:italic>in situ<\/jats:italic>\n                    . This analysis points out that multiple types of T lymphocytes have to be targeted for therapeutic regeneration of tolerance in arthritis.\n                  <\/jats:p>","DOI":"10.1002\/eji.202048797","type":"journal-article","created":{"date-parts":[[2020,12,10]],"date-time":"2020-12-10T12:59:08Z","timestamp":1607605148000},"page":"915-929","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":40,"title":["Antigen\u2010driven PD\u20101\n                    <sup>+<\/sup>\n                    <i>TOX<\/i>\n                    <sup>+<\/sup>\n                    <i>BHLHE40<\/i>\n                    <sup>+<\/sup>\n                    and PD\u20101\n                    <sup>+<\/sup>\n                    <i>TOX<\/i>\n                    <sup>+<\/sup>\n                    <i>EOMES<\/i>\n                    <sup>+<\/sup>\n                    T lymphocytes regulate juvenile idiopathic arthritis\n                    <i>in situ<\/i>"],"prefix":"10.1002","volume":"51","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1705-5302","authenticated-orcid":false,"given":"Patrick","family":"Maschmeyer","sequence":"first","affiliation":[{"name":"Deutsches Rheuma\u2010Forschungszentrum (DRFZ) Institute of the Leibniz Association  Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9330-3689","authenticated-orcid":false,"given":"Gitta Anne","family":"Heinz","sequence":"additional","affiliation":[{"name":"Deutsches Rheuma\u2010Forschungszentrum (DRFZ) Institute of the Leibniz Association  Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6089-4769","authenticated-orcid":false,"given":"Christopher Mark","family":"Skopnik","sequence":"additional","affiliation":[{"name":"Charit\u00e9 \u2010 Universit\u00e4tsmedizin Berlin corporate member of Freie Universit\u00e4t Berlin, 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