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Impaired T cell receptor signaling in HTLV-1-infected CD4+ cells from HAM/TSP patients

HAM/TSP patients show increased HTLV-1 proviral load in peripheral blood mononuclear cells (PBMCs), however, little is known about the character of HTLV-1-infected cells. It has been considered that the immune system of HTLV-1-infected individuals are impaired, however, the details are unknown. Here, we investigated HTLV-1-infected cells from HAM/TSP patients for their surface markers and immune function. PBMCs were obtained from the patients and cultured for several hours. HTLV-1-infected cells were identified by detection of intracellular HTLV-1 Tax protein. The Tax-positive, HTLV-1-infected cells showed a phenotype of CD2+CD4+CD5+CD26- CD45RO+CD45RA- CCR4+CCR7- and a reduced expression of T cell receptor (TCR) and CD3 antigen. Next, PBMCs were stimulated with CD3 antibody and TCR signaling was detected by phospho-specific antibodies for Lck and ZAP70, which are early signaling molecules of TCR. The degree of phosphorylation in whole CD4+ cells from HAM/TSP patients were lower than that from normal controls. In addition, Tax-positive CD4+ cells showed reduced phosphorylation of these molecules compared to Tax-negative CD4+ cells in HAM/TSP patients. Finally, cytomegalovirus (CMV)-specific, HTLV-1-infected CD4+ cells showed a decreased production of interferon-gamma by stimulation of CMV antigens compared to CMV-specific, non-infected cells in the patients. These results indicate that HTLV-1-infected cells reduced expression of TCR/CD3 complex in HAM/TSP patients, resulting in a reduction in TCR signaling and impaired immune function.

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Correspondence to Ryuji Kubota.

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This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver ( applies to the data made available in this article, unless otherwise stated.

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Kubota, R., Takashima, H. & Izumo, S. Impaired T cell receptor signaling in HTLV-1-infected CD4+ cells from HAM/TSP patients. Retrovirology 11 (Suppl 1), P65 (2014).

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