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Diabetes prevention strategies targeting different cytokines with antibodies in combination with a T cell antibody, anti-TCR, have been assessed for therapy success in the LEW.1AR1-<jats:italic>iddm<\/jats:italic>(IDDM) rat, an animal model of human T1D. Immediately after diabetes manifestation, antibody combination therapies were initiated over 5 days with anti-TNF-\u03b1 (tumour necrosis factor), anti-IL-1\u03b2 (interleukin), or anti-IFN-\u03b3 (interferon) together with anti-TCR for the reversal of the diabetic metabolic state in the IDDM rat. Anti-TCR alone showed only a very limited therapy success with respect to a reduction of immune cell infiltration and beta cell mass regeneration. Anti-TCR combinations with anti-IL-1\u03b2 or anti-IFN-\u03b3 were also not able to abolish the increased beta cell apoptosis rate and the activated immune cell infiltrate leading to a permanent beta cell loss. In contrast, all anti-TCR combinations with anti-TNF-\u03b1 provided sustained therapy success over 60 to 360 days. The triple combination of anti-TCR with anti-TNF-\u03b1 plus anti-IL-1\u03b2 was most effective in regaining sustained normoglycaemia with an intact islet structure in a completely infiltration-free pancreas and with a normal beta cell mass. Besides the triple combination, the double antibody combination of anti-TCR with anti-TNF-\u03b1 proved to be the most suited therapy for reversal of the T1D metabolic state due to effective beta cell regeneration in an infiltration free pancreas.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key messages<\/jats:title><jats:p><jats:list list-type=\"bullet\"><jats:list-item><jats:p>Anti-TCR is a cornerstone in combination therapy for autoimmune diabetes reversal.<\/jats:p><\/jats:list-item><jats:list-item><jats:p>The combination of anti-TCR with anti-TNF-\u03b1 was most effective in reversing islet immune cell infiltration.<\/jats:p><\/jats:list-item><jats:list-item><jats:p>Anti-TCR combined with anti-IL-1\u03b2 was not effective in this respect.<\/jats:p><\/jats:list-item><jats:list-item><jats:p>The combination of anti-TCR with anti-TNF-\u03b1 showed a sustained effect over 1 year.<\/jats:p><\/jats:list-item><\/jats:list><\/jats:p><\/jats:sec>","DOI":"10.1007\/s00109-020-01941-8","type":"journal-article","created":{"date-parts":[[2020,6,30]],"date-time":"2020-06-30T14:02:52Z","timestamp":1593525772000},"page":"1125-1137","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Translation of curative therapy concepts with T cell and cytokine antibody combinations for type 1 diabetes reversal in the IDDM rat"],"prefix":"10.1007","volume":"98","author":[{"given":"Anne","family":"J\u00f6rns","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tanja","family":"Arndt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shinichiro","family":"Yamada","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daichi","family":"Ishikawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshiaki","family":"Yoshimoto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taivankhuu","family":"Terbish","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dirk","family":"Wedekind","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter H.","family":"van der Meide","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2125-8193","authenticated-orcid":false,"given":"Sigurd","family":"Lenzen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,6,30]]},"reference":[{"issue":"9911","key":"1941_CR1","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1016\/S0140-6736(13)60591-7","volume":"383","author":"MA Atkinson","year":"2014","unstructured":"Atkinson MA, Eisenbarth GS, Michels AW (2014) Type 1 diabetes. 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