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One patient had deteriorating pulmonary involvement, and the second patient had developed disabling skin disease with multiple ulcers and gangrene. Both patients showed improvement concomitant with almost complete elimination of CD4+ and CD8+ T lymphocytes. Regeneration of peripheral T cells required 60\u201390 days and was followed by a long\u2010term inversion of the CD4:CD8 ratio. The persistent therapeutic effect in both patients correlated with the lack of CD4+ T cells and the predominance of CD8+ T cells. This suggests a crucial role of T cell immunity in the pathogenesis of systemic sclerosis. In vitro studies of regenerating T cells demonstrated that CD4+ helper\/inducer cells were functionally competent. Alterations in the composition of the CD8+ population may explain the prolonged suppression of CD4+ T cells observed during the period of therapeutic benefit.<\/jats:p>","DOI":"10.1002\/art.1780330408","type":"journal-article","created":{"date-parts":[[2007,2,14]],"date-time":"2007-02-14T23:29:27Z","timestamp":1171495767000},"page":"511-519","source":"Crossref","is-referenced-by-count":16,"title":["Long\u2010term immunomodulatory effects of t lymphocyte depletion in patients with systemic sclerosis"],"prefix":"10.1002","volume":"33","author":[{"given":"J\u00f6rg J.","family":"Goronzy","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cornelia M.","family":"Weyand","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2005,12,9]]},"reference":[{"key":"e_1_2_1_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/0049-0172(82)90055-5"},{"key":"e_1_2_1_3_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.1780270607"},{"key":"e_1_2_1_4_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.149.6.1326"},{"key":"e_1_2_1_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(18)61587-X"},{"key":"e_1_2_1_6_2","doi-asserted-by":"crossref","first-page":"9049","DOI":"10.1016\/S0021-9258(19)84486-1","article-title":"Immune interferon suppresses levels of procollagen mRNA and type II collagen synthesis in cultured human articular and costal chondrocytes","volume":"261","author":"Goldring MB","year":"1986","journal-title":"J Biol Chem"},{"issue":"4","key":"e_1_2_1_7_2","first-page":"S21","article-title":"Lymphotoxin (tumor necrosis factor\u2010\u03b2) induces and augments collagen, collagenase and prostaglandin E2 production by fibroblasts: potential role in inflammatory and fibrotic processes (abstract)","volume":"31","author":"Amento EP","year":"1988","journal-title":"Arthritis Rheum"},{"key":"e_1_2_1_8_2","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-97-5-652"},{"key":"e_1_2_1_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/0167-5699(88)91212-1"},{"key":"e_1_2_1_10_2","doi-asserted-by":"crossref","first-page":"1922","DOI":"10.4049\/jimmunol.135.3.1922","article-title":"Characteristics of a monoclonal antibody (WT\u201031) that recognizes a common epitope on the human T cell receptor for antigen","volume":"135","author":"Spits H","year":"1985","journal-title":"J Immunol"},{"key":"e_1_2_1_11_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.1780230510"},{"key":"e_1_2_1_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(18)49315-5"},{"key":"e_1_2_1_13_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.1780230602"},{"key":"e_1_2_1_14_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM197611182952101"},{"key":"e_1_2_1_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/0002-9343(80)90380-0"},{"key":"e_1_2_1_16_2","first-page":"462","article-title":"The clinical value of antilymphocyte antibodies","volume":"13","author":"Cosimi AB","year":"1981","journal-title":"Transplant Proc"},{"key":"e_1_2_1_17_2","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1182\/blood.V44.1.57.57","article-title":"Treatment of established human graft\u2010versus\u2010host disease by antilymphocyte globulin","volume":"44","author":"Storb R","year":"1974","journal-title":"Blood"},{"key":"e_1_2_1_18_2","volume-title":"Aplastic Anemia: Stem Cell Biology and Advances in Treatment","author":"Young N","year":"1984"},{"key":"e_1_2_1_19_2","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-106-1-56"},{"key":"e_1_2_1_20_2","doi-asserted-by":"crossref","first-page":"217","DOI":"10.4049\/jimmunol.96.2.217","article-title":"Studies on heterologous anti\u2010lymphocyte serum in mice: in vitro and in vivo properties","volume":"96","author":"Gray JG","year":"1966","journal-title":"J Immunol"},{"key":"e_1_2_1_21_2","doi-asserted-by":"publisher","DOI":"10.1002\/eji.1830121116"},{"key":"e_1_2_1_22_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.128.6.1281"},{"key":"e_1_2_1_23_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI113675"},{"issue":"4","key":"e_1_2_1_24_2","first-page":"S33","article-title":"Treatment of systemic sclerosis with antithy mocyte globulin (abstract)","volume":"31","author":"Zashin SJ","year":"1989","journal-title":"Arthritis Rheum"}],"container-title":["Arthritis &amp; 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