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The molecular mechanisms underlying the therapeutic efficacy are unknown, but may involve myeloid\u2010derived suppressor cells (MDSCs). AA\u2010affected mice were treated with squaric acid dibutyl ester (SADBE). The immunoreactivity of SADBE\u2010treated AA lymphocytes and of AA lymphocytes co\u2010cultured with SADBE\u2010induced MDSCs was analyzed. The curative effect of SADBE was abolished by all\u2010transretinoic acid, which drives MDSCs into differentiation, confirming a central role for MDSCs in therapeutic SADBE treatment. SADBE and SADBE\u2010induced MDSCs strongly interfered with sustained autoreactive T\u2010cell proliferation in response to AA skin lysate (autoantigen), which was accompanied by weak \u03b6\u2010chain down\u2010regulation and strongly impaired Lck activation. In contrast, activation of the mitochondrial apoptosis pathway and blockade of the anti\u2010apoptotic PI3K\/Akt pathway by SADBE\u2010induced MDSCs did not require T\u2010cell receptor engagement. Apoptosis induction correlated with high TNF\u2010\u03b1 expression in SADBE\u2010induced MDSCs and elevated TNFRI levels in AA lymphocytes. SADBE\u2010induced MDSCs interfere with persisting autoreactive T\u2010cell proliferation and promote apoptosis of these T cells, which qualifies MDSCs induced and maintained by chronic delayed type hypersensitivity reactions as promising therapeutics in organ\u2010related autoimmune diseases.<\/jats:p>","DOI":"10.1002\/eji.201141696","type":"journal-article","created":{"date-parts":[[2011,7,4]],"date-time":"2011-07-04T13:54:58Z","timestamp":1309787698000},"page":"2871-2882","source":"Crossref","is-referenced-by-count":16,"title":["Delayed type hypersensitivity\u2010induced myeloid\u2010derived suppressor cells regulate autoreactive T cells"],"prefix":"10.1002","volume":"41","author":[{"given":"Vibhuti","family":"Singh","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ulrike","family":"Mueller","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pia","family":"Freyschmidt\u2010Paul","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Margot","family":"Z\u00f6ller","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2011,8,30]]},"reference":[{"key":"e_1_2_6_2_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1087-0024.2003.00802.x"},{"key":"e_1_2_6_3_2","doi-asserted-by":"publisher","DOI":"10.1159\/000131412"},{"key":"e_1_2_6_4_2","doi-asserted-by":"publisher","DOI":"10.1159\/000131749"},{"key":"e_1_2_6_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature09114"},{"key":"e_1_2_6_6_2","first-page":"327","article-title":"Diphencyprone immunotherapy alters anti\u2010hair follicle antibody status in patients with alopecia areata","volume":"12","author":"Tobin D. 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