Spontaneous proliferation of peripheral blood lymphocytes increased in patients with HTLV‐I‐associated myelopathy

Itoyama, Yasuto; Minato, Seiichiro; Kira, Jun‐ichi; Goto, I.; Sato, Haruhiko; Okochi, Kazuo; Yamamoto, Naoki

doi:10.1212/wnl.38.8.1302

Cited by 194 publications

(108 citation statements)

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“…HTLV-I induces proliferation of both the host cell (Itoyama et al 1988) and bystander lymphocytes (Wucherpfennig et al 1992). It is likely (Wodarz et al 1999b) that both processes contribute to maintaining the basic reproductive ratio of the virus (R 0 , the average number of cells that is infected by each HTLV-I-positive lymphocyte at the start of the infection) above unity, and so allow persistence of the infection.…”

Section: Discussionmentioning

confidence: 99%

Genetic control and dynamics of the cellular immune response to the human T–cell leukaemia virus, HTLV–I

Bangham

Hall

Jeffery

et al. 1999

Phil. Trans. R. Soc. Lond. B

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About 1% of people infected with the human T-cell leukaemia virus, type 1 (HTLV-I) develop a disabling chronic in£ammatory disease of the central nervous system known as HTLV-I-associated myelopathy/ tropical spastic paraparesis (HAM/TSP). Patients with HAM/TSP have a vigorous immune response to HTLV-I, and it has been widely suggested that this immune response, particularly the HTLV-I-speci¢c cytotoxic T-lymphocyte (CTL) response, causes the tissue damage that is seen in HAM/TSP. In this paper we summarize recent evidence that a strong CTL response to HTLV-I does in fact protect against HAM/TSP by reducing the proviral load of HTLV-I. We conclude that HTLV-I is persistently replicating at a high level, despite the relative constancy of its genome sequence. These results imply that antiretroviral drugs could reduce the risk of HAM/TSP by reducing the viral load, and that an e¡ective anti-HTLV-I vaccine should elicit a strong CTL response to the virus. The dynamic nature of the infection also has implications for the epidemiology and the evolution of HTLV-I.

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Section: Discussionmentioning

confidence: 99%

Genetic control and dynamics of the cellular immune response to the human T–cell leukaemia virus, HTLV–I

Bangham

Hall

Jeffery

et al. 1999

Phil. Trans. R. Soc. Lond. B

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“…In the early phases of ATL and in HAM/TSP, there is an abnormal proliferation of T cells. In ex vivo cultures, T cells of HAM/TSP patients undergo spontaneous proliferation in the absence of exogenous cytokine or growth factors (41,42). The spontaneous proliferation of these T cells has been attributed to the Tax-induced overexpression of IL-2 and IL-2R␣ which results in the establishment of autocrine and paracrine loops (35,43,44).…”

Section: Human T Cell Lymphotropic Virus Type I Tax Activates Il-15r␣mentioning

confidence: 99%

Human T Cell Lymphotropic Virus Type I Tax Activates IL-15Rα Gene Expression Through an NF-κB Site

Mariner

Lantz

Waldmann

et al. 2001

The Journal of Immunology

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IL-15 mRNA levels are increased in diseases caused by human T cell lymphotropic virus type I (HTLV-I). In this study, we demonstrated that IL-15Rα, the IL-15-specific binding receptor, mRNA and protein levels were also elevated in HTLV-I-infected cells. We showed that transient HTLV-I Tax expression lead to increased IL-15Rα mRNA levels. In addition, by using a reporter construct that bears the human IL-15Rα promoter, we demonstrated that Tax expression increased promoter activity by at least 4-fold. Furthermore, using promoter deletion constructs and gel shift analysis, we defined a functional NF-κB-binding motif in the human IL-15Rα promoter, suggesting that Tax activation of IL-15Rα is due, in part, to the induction of NF-κB. These data indicate that IL-15Rα is transcriptionally regulated by the HTLV-I Tax protein through the action of NF-κB. These findings suggest a role for IL-15Rα in aberrant T cell proliferation observed in HTLV-I-associated diseases.

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“…ATL is a malignancy of helper T lymphocytes whereas HAM/TSP is a myelopathy which shares some of the characteristics of multiple sclerosis. The peripheral blood mononuclear cells of infected individuals undergo spontaneous proliferation in vitro (Itoyama et al, 1988;Jacobson et al, 1988;Tendler et al, 1990) which may result from the activation of expression of interleukin 2 (IL-2) and its receptor (IL-2R) by HTLV-1 (Siekevitz et al, 1987a). The alteration of normal cellular function by HTLV-1 has been proposed to be associated with the expression of viral proteins such as the trans-activator Tax which can induce IL-2R expression (Tendler et al, 1990).…”

Section: Introductionmentioning

confidence: 99%

Calcium-mediated inhibition of phorbol ester and Tax trans-activation of the human T cell leukaemia virus type 1

Copeland

Haaksma

Goudsmit

et al. 1994

Journal of General Virology

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Human Jurkat T cells containing a stably integrated human T cell leukaemia virus type 1 (HTLV-1) long terminal repeat (LTR) reporter gene construct were used to study the role of calcium-dependent cellular activation pathways in LTR trans-activation. Treatment of these cells with the calcium ionophore ionomycin resulted in a reduced basal response of the LTR and reduced responses to 12-O-tetradecanoylphorbol-13-acetate-and Tax-mediated trans-activation. This effect was also observed for virus production in the HTLV-1-producing T cell line MT-2. Experiments designed to determine the events underlying this inhibition, using inhibitors of calcium-related events, revealed that the ionomycininduced repression of the LTR was alleviated in all cases by cyclosporin A. This compound was also effective in preventing the ionomycin-induced reduction in virus production in MT-2 cells. These results suggest a role for calcium-related events in the down-regulation of HTLV-1 expression.

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Spontaneous proliferation of peripheral blood lymphocytes increased in patients with HTLV‐I‐associated myelopathy

Cited by 194 publications

References 0 publications

Genetic control and dynamics of the cellular immune response to the human T–cell leukaemia virus, HTLV–I

Genetic control and dynamics of the cellular immune response to the human T–cell leukaemia virus, HTLV–I

Human T Cell Lymphotropic Virus Type I Tax Activates IL-15Rα Gene Expression Through an NF-κB Site

Calcium-mediated inhibition of phorbol ester and Tax trans-activation of the human T cell leukaemia virus type 1

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