{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,23]],"date-time":"2025-09-23T13:38:58Z","timestamp":1758634738666},"reference-count":56,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2005,12,12]],"date-time":"2005-12-12T00:00:00Z","timestamp":1134345600000},"content-version":"vor","delay-in-days":3116,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Arthritis &amp; Rheumatism"],"published-print":{"date-parts":[[1997,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p><jats:italic>Objective.<\/jats:italic> To examine the in vivo mechanisms of suppression of T lymphocyte function in patients with Beh\u00e7et's disease (BD) undergoing long\u2010term treatment with tacrolimus (FK\u2010506).<\/jats:p><jats:p><jats:italic>Methods.<\/jats:italic> Intracellular proteins were analyzed by immunoprecipitation and Western blotting. Messenger RNA expression was studied by a polymerase chain reaction\u2014based technique.<\/jats:p><jats:p><jats:italic>Results.<\/jats:italic> Interleukin\u20102 production was suppressed in patients treated with tacrolimus. This suppression was found to be due to inhibition of interactions between activated calcineurin (Cn) and nuclear factor of activated T cells (NF\u2010AT), inhibition of cleavage of the autoinhibitory domain of the CnA subunit, and inhibition of heterodimer formation by CnA and CnB sub\u2010units, resulting in the absence of NF\u2010AT in nuclei of the T cells. We found that T lymphocytes in some BD patients treated with tacrolimus had reduced amounts of FK\u2010506 binding protein (FKBP) in their cytoplasm.<\/jats:p><jats:p><jats:italic>Conclusion.<\/jats:italic> Tacrolimus reduces the Cn activity of T cells in vivo by the cumulative effects of several distinct mechanisms. It is plausible that reduced amounts of FKBP may be associated with diminished clinical efficacy in some BD patients receiving prolonged treatment with tacrolimus.<\/jats:p>","DOI":"10.1002\/art.1780400622","type":"journal-article","created":{"date-parts":[[2007,2,14]],"date-time":"2007-02-14T12:42:54Z","timestamp":1171456974000},"page":"1157-1167","source":"Crossref","is-referenced-by-count":21,"title":["In vivo mechanisms for the inhibition of T lymphocyte activation by long\u2010term therapy with tacrolimus 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