High frequency of CD4+FoxP3+ cells in HTLV-1 infection: inverse correlation with HTLV-1–specific CTL response

Toulza, Frédéric; Heaps, Adrian; Tanaka, Yuetsu; Taylor, Graham P.; Bangham, Charles R. M.

doi:10.1182/blood-2007-10-118539

Cited by 112 publications

(142 citation statements)

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“…We found a highly significant negative association between Tax and Foxp3 in the T cells of HAM/TSP patients. Foxp3 mRNA in HAM/TSP patients was lower than in non-infected controls (Table 1), in agreement with data reported by other investigators (10,27). In addition, we detected a direct correlation between the levels of Foxp3, CTLA-4 and GITR.…”

Section: Discussionsupporting

confidence: 92%

“…These observations suggest that dysregulation of TGF-β signaling and silencing of downstream TGF-β-responsive genes, including Foxp3, could be involved in the pathogenesis of HAM/TSP. However, other studies have found no correlation of IL-10 and TGF-β1 mRNA with Foxp3 levels, or their correlation with HTLV-1-infected cell lysis (10). CD4 + Foxp3 + cells probably exert their regulatory effect on HTLV-1-specific CD8 (+) T cells by a cell contact mechanism, with or without the involvement of cytokines.…”

Section: Discussionmentioning

confidence: 85%

“…In T cells of HAM/TSP patients, this phenomenon has been suggested to be an important mechanism of viral pathogenesis (27). Within the context of HTLV-I, the frequency of non-infected CD4 + CD25 + Treg lymphocytes can be an important marker of the efficiency of T cell-mediated immune control (10). The transfection of the HTLV-1 tax gene into purified CD4 + CD25 + T cells from non-infected healthy donors caused a decrease in Foxp3 expression.…”

Section: Discussionmentioning

confidence: 99%

“…High levels of proviral DNA or Tax mRNA have been detected in patients with important neurological involvement when compared to asymptomatic carriers (10,29,30). Tax mRNA has been suggested to be a predictor of HAM/TSP progression (7).…”

Section: Discussionmentioning

confidence: 99%

“…In addition, Tax-specific inhibition of Foxp3 mRNA expression may be associated with the suppression of CD4 + CD25 + T cells that in turn might be related to the suppression of Treg function (9,10). Foxp3 is critical for the development and function of Treg, with Foxp3 reduction and Treg dysfunction being associated with autoimmune diseases such as multiple sclerosis, myasthenia gravis, and type 1 diabetes (11)(12)(13).…”

Section: Introductionmentioning

confidence: 99%

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In vivo fluctuation of Tax, Foxp3, CTLA-4, and GITR mRNA expression in CD4+CD25+ T cells of patients with human T-lymphotropic virus type 1-associated myelopathy

Ramı́rez

Cartier

Rodriguez

et al. 2010

Braz J Med Biol Res

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Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 85%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

In vivo fluctuation of Tax, Foxp3, CTLA-4, and GITR mRNA expression in CD4+CD25+ T cells of patients with human T-lymphotropic virus type 1-associated myelopathy

Ramı́rez

Cartier

Rodriguez

et al. 2010

Braz J Med Biol Res

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Paving the way for thermophilic bioethanol production

2013

Biotech & Bioengineering

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CTL quality and the control of human retroviral infections

Bangham

2009

Eur J Immunol

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127

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The CTL response plays a central part in deciding the outcome of viral infections. Evidence from host and viral genetics, gene expression microarrays and assays of T-cell phenotype and function indicate that individual differences in the efficiency of the virus-specific CTL response strongly determine the outcome of infection with the human retroviruses HTLV-1 and HIV-1. It is now believed that differences in anti-viral CTL efficiency or ''quality'' at the single-cell level are critical in determining the efficacy of the host response to viruses. However, it is difficult to identify and quantify the reasons for this apparent individual variation in CTL efficiency, because of the chronic course of infection and the dynamical complexity of the equilibrium that is established between the virus and the host immune response. Specifically, it is unclear whether the observed variations among infected hosts, i.e. in the frequency, phenotype and function or quality of T cells, are the causes or effects -or both -of the variation in the efficiency of virus control.Key words: CTL efficiency . Functional avidity . HIV-1 . HTLV-1 . Polyfunctionality IntroductionThe CD8 + CTL is an essential component of an effective host immune response to all viral infections [1][2][3][4]. CD8 + T cells suppress viral replication by three main effector mechanisms: production of IFN-g, lysis of virus-infected ''target'' cells via Fas-FasL interaction, or lysis of target cells by the delivery of granzymes and perforin to the infected cell. Of these, the third mechanism is the most rapid and is usually the most important in anti-viral defense.The human retroviruses HIV-1 and HTLV-1 cause lifelong persistent infection in the host. In each case, a proportion of the infected hosts remain asymptomatic. Untreated HIV-1 infection usually causes death from AIDS in about 10 years, but the rate of progression of the disease varies widely among individuals. Moreover, a small proportion of infected hosts -about 0.3% -seem to control HIV-1 replication sufficiently well to remain asymptomatic indefinitely. Such ''HIV controllers'' or ''elite controllers'', usually defined as those who maintain a plasma viral load o50 copies/mL, have recently been intensely investigated in an attempt to identify what constitutes an effective host immune response to the virus [5].HTLV-1 similarly establishes a lifelong persistent infection but, in contrast to HIV-1, over 90% of infected individuals remain indefinitely asymptomatic. Between 1 and 6% develop an aggressive malignancy of CD4 + T cells known as adult T-cell leukemia, which is typically fatal within one year, and a further 0.1-2% develop a disabling chronic inflammatory disease of the central nervous system known as HTLV-1-associated myelopathy/ tropical spastic paraparesis (HAM/TSP). In both HTLV-1 and HIV-1 infection, a dynamic equilibrium is established between persistent viral replication and the host immune response. In each infection, the prevalence and incidence of disease are strongly correlated with the s...

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High frequency of CD4+FoxP3+ cells in HTLV-1 infection: inverse correlation with HTLV-1–specific CTL response

Cited by 112 publications

References 49 publications

In vivo fluctuation of Tax, Foxp3, CTLA-4, and GITR mRNA expression in CD4+CD25+ T cells of patients with human T-lymphotropic virus type 1-associated myelopathy

In vivo fluctuation of Tax, Foxp3, CTLA-4, and GITR mRNA expression in CD4+CD25+ T cells of patients with human T-lymphotropic virus type 1-associated myelopathy

Paving the way for thermophilic bioethanol production

CTL quality and the control of human retroviral infections

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