Human T‐lymphotropic virus type I‐associated myelopathy and tax gene expression in CD4<sup>+</sup> T lymphocytes

Moritoyo, Takashi; Reinhart, Todd A.; Moritoyo, Hiroyoko; Satô, Eiichi; Izumo, Shuji; Osame, Mitsuhiro; Haase, Ashley T.

doi:10.1002/ana.410400114

Cited by 99 publications

(61 citation statements)

References 28 publications

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“…Within the CNS, CD4 T cells represent at least one cell type where studies have con®rmed the presence of proviral DNA by PCR-in situ hybridization and expression of viral gene products by in situ hybridization (Hara et al, 1994;Moritoyo et al, 1996). The other cell type that has been found to be infected with HTLV-I in the CNS is the resident astrocyte population (Lehky et al, 1995).…”

Section: Overview Of the Pathogenic Processmentioning

confidence: 99%

“…Although controversial, other potential cell types harboring HTLV-I proviral DNA in the CNS may include macrophages, microglial cells, oligodendrocytes, and neurons. However, HTLV-I proviral DNA or viral RNA has not yet been conclusively demonstrated in these cell types utilizing PCR-in situ hybridization and in situ hybridization, respectively (Hara et al, 1994;Kuroda et al, 1994;Lehky et al, 1995;Moritoyo et al, 1996). Interestingly, HTLV-I infection of PB monocytes and dendritic cells has been shown in vivo and in vitro (Koralnik et al, 1992;Macatonia et al, 1992;Koyanagi et al, 1993;Makino et al, 1999), suggesting that perivascular macrophages and microglial cells derived from PB monocytes may also be infected.…”

Section: Overview Of the Pathogenic Processmentioning

confidence: 99%

“…Second, microglial cells are susceptible to infection with HTLV-I in vitro (Hoffman et al, 1992), suggesting that if these cells come into contact with in®ltrating HTLV-I CD4 T cells or HTLV-I astrocytes, cell±cell contact could result in transmission of HTLV-I to this resident CNS cell population. Third, in situ hybridization coupled with immunohistochemical analysis have shown that HTLV-I-speci®c RNA expression co-localized mainly to CD4 T cells or GFAP astrocytes (Lehky et al, 1995;Moritoyo et al, 1996). However, a signi®cant amount of probe hybridized to cell types that remained unidenti®able.…”

Section: Overview Of the Pathogenic Processmentioning

confidence: 99%

“…T cells, CD8 T cells, and activated macrophages and microglial cells in and around the sites of CNS lesions¯uctuate with duration of disease (Umehara et al, 1993;Kubota et al, 1994;Moritoyo et al, 1996). Therefore, the numbers of HTLV-I cells in the CNS would also be expected to change during this transition.…”

Section: Overview Of the Pathogenic Processmentioning

confidence: 99%

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Human T cell leukemia virus type I and neurologic disease: Events in bone marrow, peripheral blood, and central nervous system during normal immune surveillance and neuroinflammation

Grant

Barmak

Alefantis

et al. 2002

Journal Cellular Physiology

101

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Human T cell lymphotropic/leukemia virus type I (HTLV‐I) has been identified as the causative agent of both adult T cell leukemia (ATL) and HTLV‐I‐associated myelopathy/tropical spastic paraparesis (HAM/TSP). Although the exact sequence of events that occur during the early stages of infection are not known in detail, the initial route of infection may predetermine, along with host, environmental, and viral factors, the subset of target cells and/or the primary immune response encountered by HTLV‐I, and whether an HTLV‐I‐infected individual will remain asymptomatic, develop ATL, or progress to the neuroinflammatory disease, HAM/TSP. Although a large number of studies have indicated that CD4+ T cells represent an important target for HTLV‐I infection in the peripheral blood (PB), additional evidence has accumulated over the past several years demonstrating that HTLV‐I can infect several additional cellular compartments in vivo, including CD8+ T lymphocytes, PB monocytes, dendritic cells, B lymphocytes, and resident central nervous system (CNS) astrocytes. More importantly, extensive latent viral infection of the bone marrow, including cells likely to be hematopoietic progenitor cells, has been observed in individuals with HAM/TSP as well as some asymptomatic carriers, but to a much lesser extent in individuals with ATL. Furthermore, HTLV‐I+ CD34+ hematopoietic progenitor cells can maintain the intact proviral genome and initiate viral gene expression during the differentiation process. Introduction of HTLV‐I‐infected bone marrow progenitor cells into the PB, followed by genomic activation and low level viral gene expression may lead to an increase in proviral DNA load in the PB, resulting in a progressive state of immune dysregulation including the generation of a detrimental cytotoxic Tax‐specific CD8+ T cell population, anti‐HTLV‐I antibodies, and neurotoxic cytokines involved in disruption of myelin‐producing cells and neuronal degradation characteristic of HAM/TSP. J. Cell. Physiol. 190: 133–159, 2002. © 2002 Wiley‐Liss, Inc.

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Section: Overview Of the Pathogenic Processmentioning

confidence: 99%

Section: Overview Of the Pathogenic Processmentioning

confidence: 99%

Section: Overview Of the Pathogenic Processmentioning

confidence: 99%

Section: Overview Of the Pathogenic Processmentioning

confidence: 99%

See 2 more Smart Citations

Human T cell leukemia virus type I and neurologic disease: Events in bone marrow, peripheral blood, and central nervous system during normal immune surveillance and neuroinflammation

Grant

Barmak

Alefantis

et al. 2002

Journal Cellular Physiology

101

View full text Add to dashboard Cite

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“…(i) There are few if any host cells in the in£ammatory lesions that are infected with HTLV-I, other than the invading CD4+ T cells (Kira et al 1991(Kira et al , 1992Ohara et al 1992;Hara et al 1994;Lehky et al 1995;Moritoyo et al 1996). It is therefore unlikely that HAM/ TSP is caused by a direct host immune attack against HTLV-I-infected cells which are normally resident in the CNS.…”

Section: Do Host or Viral Factors Determine The Equilibrium Proviral mentioning

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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Neuronal molecular mimicry in immune‐mediated neurologic disease

Levin

Krichavsky

Berk

et al. 1998

Annals of Neurology

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Molecular mimicry is implicated in the pathogenesis of autoimmune diseases such as diabetes mellitus, rheumatoid arthritis, and multiple sclerosis (MS). Cellular and antibody-mediated immune responses to shared viral-host antigens have been associated with the development of disease in these patients. Patients infected with human T-lymphotropic virus type I (HTLV-I) develop HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP), an immune-mediated disorder of the central nervous system (CNS) that resembles some forms of MS. Damage to neuronal processes in the CNS of HAM/TSP patients is associated with an activated cellular and antibody-mediated immune response. In this study, IgG isolated from HAM/TSP patients was immunoreactive with uninfected neurons and this reactivity was HTLV-I specific. HAM/TSP IgG stained uninfected neurons in human CNS and cell lines but not nonneuronal cells. Neuronal western blots showed IgG reactivity with a single 33-kd band in all HAM/TSP patients tested. By contrast, no neuron-specific IgG reactivity could be demonstrated from HTLV-I seronegative controls and, more important, from HTLV-I seropositive, neurologically asymptomatic individuals. Both immunocytochemical staining and western blot reactivity were abolished by preincubating HAM/TSP IgG with HTLV-I protein lysate but not by control proteins. Staining of CNS tissue by a monoclonal antibody to HTLV-I tax (an immunodominant HTLV-I antigen) mimicked HAM/TSP IgG immunoreactivity. There was no staining by control antibodies. Absorption of HAM/TSP IgG with recombinant HTLV-I tax protein or preincubation of CNS tissue with the monoclonal antibody to HTLV-I tax abrogated the immunocytochemical and western blot reactivity of HAM/TSP IgG. Furthermore, in situ human IgG localized to neurons in HAM/TSP brain but not in normal brain. These data indicate that HAM/TSP patients develop an antibody response that targets uninfected neurons, yet reactivity is blocked by HTLV-I, suggesting viral-specific autoimmune reactivity to the CNS, the damaged target organ in HAM/TSP.

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Human T‐lymphotropic virus type I‐associated myelopathy and tax gene expression in CD4⁺ T lymphocytes

Cited by 99 publications

References 28 publications

Human T cell leukemia virus type I and neurologic disease: Events in bone marrow, peripheral blood, and central nervous system during normal immune surveillance and neuroinflammation

Human T cell leukemia virus type I and neurologic disease: Events in bone marrow, peripheral blood, and central nervous system during normal immune surveillance and neuroinflammation

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

Neuronal molecular mimicry in immune‐mediated neurologic disease

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Human T‐lymphotropic virus type I‐associated myelopathy and tax gene expression in CD4+ T lymphocytes

Cited by 99 publications

References 28 publications

Human T cell leukemia virus type I and neurologic disease: Events in bone marrow, peripheral blood, and central nervous system during normal immune surveillance and neuroinflammation

Human T cell leukemia virus type I and neurologic disease: Events in bone marrow, peripheral blood, and central nervous system during normal immune surveillance and neuroinflammation

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

Neuronal molecular mimicry in immune‐mediated neurologic disease

Contact Info

Product

Resources

About

Human T‐lymphotropic virus type I‐associated myelopathy and tax gene expression in CD4⁺ T lymphocytes