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Rat AA was preventively treated by intraperitoneal injection of the anti-CD4 mAbs W3\/25, OX35, and RIB5\/2 (on days -1, 0, 3, and 6, i.e. 1 day before AA induction, on the day of induction [day 0], and thereafter). The effects on T-cell reactivity<jats:italic>in vivo<\/jats:italic>(delayed-type hypersensitivity),<jats:italic>ex vivo<\/jats:italic>(ConA-induced proliferation), and<jats:italic>in vitro<\/jats:italic>(mixed lymphocyte culture) were assessed. The<jats:italic>in vitro<\/jats:italic>effects of anti-CD4 preincubation on T-cell receptor (TCR)\/CD3-induced cytokine production and signal transduction were also analyzed. While preventive treatment with OX35 and W3\/25 significantly ameliorated AA from the onset, treatment with RIB5\/2 even accelerated the onset of AA by approximately 2 days (day 10), and ameliorated the arthritis only in the late phase (day 27). Differential clinical effects at the onset of AA were paralleled by a differential influence of the mAbs on T-cell functions, i.e. in comparison with OX35 and W3\/25, the 'accelerating' mAb RIB5\/2 failed to increase the delayed-type hypersentivity (DTH) to<jats:italic>Mycobacterium tuberculosis,<\/jats:italic>increased the<jats:italic>in vitro<\/jats:italic>tumor necrosis factor (TNF)-\u03b1 secretion, and more strongly induced NF-\u03baB binding activity after anti-CD4 preincubation and subsequent TCR\/CD3-stimulation. Depending on their epitope specificity, different anti-CD4 mAbs differentially influence individual proinflammatory functions of T cells. This fine regulation may explain the differential efficacy in the treatment of AA and may contribute to the understanding of such treatments in other immunopathologies.<\/jats:p>","DOI":"10.1186\/ar404","type":"journal-article","created":{"date-parts":[[2002,9,26]],"date-time":"2002-09-26T12:07:27Z","timestamp":1033042047000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Differential clinical efficacy of anti-CD4 monoclonal antibodies in rat adjuvant arthritis is paralleled by differential influence on NF-\u03baB binding activity and TNF-\u03b1 secretion of T cells"],"prefix":"10.1186","volume":"4","author":[{"given":"Dirk","family":"Pohlers","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carsten B","family":"Schmidt-Weber","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Angels","family":"Franch","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J\u00fcrgen","family":"Kuhlmann","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rolf","family":"Br\u00e4uer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Frank","family":"Emmrich","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Raimund W","family":"Kinne","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2002,4,1]]},"reference":[{"key":"404_CR1","doi-asserted-by":"publisher","first-page":"109","DOI":"10.1016\/S0925-4439(96)00079-8","volume":"1360","author":"RW Kinne","year":"1997","unstructured":"Kinne RW, Palombo-Kinne E, Emmrich F: T-cells in the pathogenesis of rheumatoid arthritis villains or accomplices?. 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