{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T14:49:04Z","timestamp":1791902944864,"version":"4.3.4"},"reference-count":37,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2005,12,9]],"date-time":"2005-12-09T00:00:00Z","timestamp":1134086400000},"content-version":"vor","delay-in-days":3752,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Arthritis &amp; Rheumatism"],"published-print":{"date-parts":[[1995,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p><jats:italic>Objective<\/jats:italic>. To examine the compartment of CD4+ T cells in patients with rheumatoid arthritis (RA) who have developed persistent lymphopenia following antibody\u2010mediated T cell depletion and to investigate why T cell depletion is of limited therapeutic efficacy.<\/jats:p><jats:p><jats:italic>Methods<\/jats:italic>. Circulating T lymphocytes from 10 patients with seropositive RA treated with the monoclonal antibody (MAb) CAMPATH\u20101H were longitudinally monitored by fluorescence\u2010activated cell sorter analysis with MAb. To assess the molecular diversity of repopulating T cells, random samples of T cell clones from the peripheral blood of 3 patients were analyzed by sequencing the T cell receptor (TCR) \u03b2 chains. At the time of recurring disease, the synovial tissue was examined by immunohistochemistry, and the repertoires of peripheral and synovial tissue T cells were compared by TCR \u03b2\u2010chain sequencing and by semiquantitative hybridization with oligonucleotides specific for the V\u2013D\u2013J\u03b2 junctional region of selected clones.<\/jats:p><jats:p><jats:italic>Results<\/jats:italic>. The reconstitution of the peripheral T cell compartment was very slow. A mean CD4+ T cell count of 105\/\u03bcl was reached 34 weeks following MAb treatment. After treatment, the percentage of CD4+ T cells with the CD45RO+ phenotype was significantly increased (<jats:italic>P<\/jats:italic> = 0.001), indicating the expansion of antigen\u2010primed memory T cells. TCR \u03b2\u2010chain sequences revealed a marked restriction in the diversity of repopulating T cells with the emergence of dominant clonotypes. Despite the low counts of peripheral CD4+ T cells, the synovial tissue was infiltrated by CD4+ T cells to a similar extent as that in RA patients not treated with MAb. Selected clonotypes that had emerged in the peripheral blood compartment dominated the repertoire of tissue\u2010infiltrating T cells in the synovium.<\/jats:p><jats:p><jats:italic>Conclusion<\/jats:italic>. In patients with RA, T cell depletion induces a long\u2010term imbalance in T cell homeostasis. Clonal proliferation of CD4+ T cells severely restricts the diversity of available T cell specificities and results in the emergence of dominant clonotypes, which accumulate in the synovial tissue despite peripheral lymphopenia.<\/jats:p>","DOI":"10.1002\/art.1780380912","type":"journal-article","created":{"date-parts":[[2007,2,15]],"date-time":"2007-02-15T02:03:14Z","timestamp":1171504994000},"page":"1242-1251","source":"Crossref","is-referenced-by-count":71,"title":["Emergence of oligoclonal t cell populations following therapeutic t cell depletion in rheumatoid arthritis"],"prefix":"10.1002","volume":"38","author":[{"given":"Michael C.","family":"Jendro","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tom","family":"Ganten","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric 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