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Human T-Lymphotropic Virus Type 1 (HTLV-1) and Regulatory T Cells in HTLV-1-Associated Neuroinflammatory Disease
Department of Rare Diseases Research, Institute of Medical Science, School of Medicine, St. Marianna University, Kawasaki 216-8511, Japan
Department of Hematology, Imamura Bun-in Hospital, Kagoshima 890-0064, Japan
Viral Immunology Section, Neuroimmunology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA
* Author to whom correspondence should be addressed.
Received: 2 June 2011; in revised form: 13 August 2011 / Accepted: 16 August 2011 / Published: 25 August 2011
Abstract: Human T-lymphotropic virus type 1 (HTLV-1) is a retrovirus that is the causative agent of adult T cell leukemia/lymphoma (ATL) and associated with multiorgan inflammatory disorders, including HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) and uveitis. HTLV-1-infected T cells have been hypothesized to contribute to the development of these disorders, although the precise mechanisms are not well understood. HTLV-1 primarily infects CD4+ T helper (Th) cells that play a central role in adaptive immune responses. Based on their functions, patterns of cytokine secretion, and expression of specific transcription factors and chemokine receptors, Th cells that are differentiated from naïve CD4+ T cells are classified into four major lineages: Th1, Th2, Th17, and T regulatory (Treg) cells. The CD4+CD25+CCR4+ T cell population, which consists primarily of suppressive T cell subsets, such as the Treg and Th2 subsets in healthy individuals, is the predominant viral reservoir of HTLV-1 in both ATL and HAM/TSP patients. Interestingly, CD4+CD25+CCR4+ T cells become Th1-like cells in HAM/TSP patients, as evidenced by their overproduction of IFN-γ, suggesting that HTLV-1 may intracellularly induce T cell plasticity from Treg to IFN-γ+ T cells. This review examines the recent research into the association between HTLV-1 and Treg cells that has greatly enhanced understanding of the pathogenic mechanisms underlying immune dysregulation in HTLV-1-associated neuroinflammatory disease.
Keywords: HTLV-1; HAM/TSP; ATL; CD4+CD25+CCR4+ T cell; regulatory T cell; exFoxp3+ cell; inflammation; immune-dysfunction
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Araya, N.; Sato, T.; Yagishita, N.; Ando, H.; Utsunomiya, A.; Jacobson, S.; Yamano, Y. Human T-Lymphotropic Virus Type 1 (HTLV-1) and Regulatory T Cells in HTLV-1-Associated Neuroinflammatory Disease. Viruses 2011, 3, 1532-1548.
Araya N, Sato T, Yagishita N, Ando H, Utsunomiya A, Jacobson S, Yamano Y. Human T-Lymphotropic Virus Type 1 (HTLV-1) and Regulatory T Cells in HTLV-1-Associated Neuroinflammatory Disease. Viruses. 2011; 3(9):1532-1548.
Araya, Natsumi; Sato, Tomoo; Yagishita, Naoko; Ando, Hitoshi; Utsunomiya, Atae; Jacobson, Steven; Yamano, Yoshihisa. 2011. "Human T-Lymphotropic Virus Type 1 (HTLV-1) and Regulatory T Cells in HTLV-1-Associated Neuroinflammatory Disease." Viruses 3, no. 9: 1532-1548.