{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T03:56:03Z","timestamp":1790913363917,"version":"4.1.0"},"reference-count":35,"publisher":"American Society of Hematology","issue":"5","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2001,9,1]]},"abstract":"<jats:p>Peripheral blood mononuclear cells (PBMCs) from patients with human T-cell lymphotropic virus type I (HTLV-I)\u2013associated myelopathy\/tropical spastic paraparesis (HAM\/TSP) proliferate spontaneously in vitro. This spontaneous lymphoproliferation (SP) is one of the immunologic hallmarks of HAM\/TSP and is considered to be an important factor related to the pathogenesis of HAM\/TSP. However, the cell populations involved in this phenomenon have not yet been definitively identified. To address this issue, the study directly evaluated proliferating cell subsets in SP with a flow cytometric method using bromodeoxyuridine and Ki-67. Although both CD4+ and CD8+ T cells proliferated spontaneously, the percentage of proliferating CD8+ T cells was 2 to 5 times higher than that of CD4+ T cells. In addition, more than 40% of HTLV-I Tax11-19\u2013specific CD8+T cells as detected by an HLA-A*0201\/Tax11-19 tetramer proliferated in culture. In spite of this expansion of HTLV-I\u2013specific CD8+ T cells, HTLV-I proviral load did not decrease. This finding will help elucidate the dynamics of in vivo virus-host immunologic interactions that permit the coexistence of high HTLV-I\u2013specific CD8+ cytotoxic T-lymphocyte responses and high HTLV-I proviral load in HAM\/TSP.<\/jats:p>","DOI":"10.1182\/blood.v98.5.1506","type":"journal-article","created":{"date-parts":[[2002,7,27]],"date-time":"2002-07-27T12:46:47Z","timestamp":1027774007000},"page":"1506-1511","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":51,"title":["In vitro spontaneous lymphoproliferation in patients with human T-cell lymphotropic virus type I\u2013associated neurologic disease: predominant expansion of CD8+ T cells"],"prefix":"10.1182","volume":"98","author":[{"given":"Jill A.","family":"Sakai","sequence":"first","affiliation":[{"name":"From the Viral Immunology Section, Neuroimmunology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masahiro","family":"Nagai","sequence":"additional","affiliation":[{"name":"From the Viral Immunology Section, Neuroimmunology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meghan B.","family":"Brennan","sequence":"additional","affiliation":[{"name":"From the Viral Immunology Section, Neuroimmunology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlos A.","family":"Mora","sequence":"additional","affiliation":[{"name":"From the Viral Immunology Section, Neuroimmunology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, 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soluble interleukin-2 receptors in patients with HTLV-I-associated myelopathy.","volume":"42","author":"Matsumoto","year":"1990","journal-title":"Am J Trop Med Hyg."},{"key":"2020021222435301100_B12","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1016\/0165-5728(89)90037-4","article-title":"In vitro modulation of lymphocyte proliferation by prednisolone and interferon-alpha in patients with HTLV-I-associated myelopathy (HAM).","volume":"23","author":"Ijichi","year":"1989","journal-title":"J Neuroimmunol."},{"key":"2020021222435301100_B13","doi-asserted-by":"crossref","first-page":"942","DOI":"10.1002\/ana.410440613","article-title":"Reduction in HTLV-I proviral load and spontaneous lymphoproliferation in HTLV-I-associated myelopathy\/tropical spastic paraparesis patients treated with humanized anti-Tac.","volume":"44","author":"Lehky","year":"1998","journal-title":"Ann 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