HTLV-1-Associated Myelopathy/Tropical Spastic Paraparesis (HAM/TSP) Inflammatory Network

Gonçalves, Denise Utsch; Proietti, Fernando Augusto; Barbosa-Stancioli, Edel Figueiredo; Martins, Marina Lobato; Ribas, João Gabriel Ramos; Martins‐Filho, Olindo Assis; Teixeira-Carvalho, Andréa; Peruhype-Magalhães, Vanessa; Carneiro-Proietti, Anna Bárbara F.

doi:10.2174/187152808785107642

Cited by 52 publications

(52 citation statements)

References 103 publications

(168 reference statements)

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“…28 During HTLV-1 infection, Th1 cells are the predominant T cell subsets infiltrating the spinal cord of HAM patients. [29][30][31][32] In agreement with prior reports, we found higher proportions of Th1 cells in HAM patients. These findings support the theoretical model of a pro-inflammatory state in HAM.…”

Section: Discussionsupporting

confidence: 92%

CD4+ T cell subsets and Tax expression in HTLV-1 associated diseases

Barros

Risco

Rodríguez

et al. 2013

Pathogens and Global Health

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Human T lymphotropic virus type 1 (HTLV-1) infection displays variable clinical manifestations. These include inflammatory diseases such as HTLV-1 associated myelopathy (HAM) or immunosuppressive conditions such as Strongyloides stercoralis hyperinfection. The viral protein, Tax causes activation and proliferation of T cells. We hypothesize that the expression of Tax in T cell subsets characterizes the clinical manifestations of HTLV-1. To test this hypothesis, we measured T helper 1 effector cells and regulatory T cells (Tregs) among Tax expressing lymphocytes from peripheral blood mononuclear cells (PBMCs) of 32 HTLV-1 infected patients with HAM, with S. stercoralis co-infection or with asymptomatic infection. We observed increased ratios of Th1/Treg among Tax expressing lymphocytes in HAM patients. These data suggest that the expression of Tax among the different target cells may explain the variable presentation of HTLV-1.

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Section: Discussionsupporting

confidence: 92%

CD4+ T cell subsets and Tax expression in HTLV-1 associated diseases

Barros

Risco

Rodríguez

et al. 2013

Pathogens and Global Health

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“…HTLV-1 infection is characterized by the production of high levels of Th1 inflammatory cytokines in blood and cerebrospinal fluid and increased levels of IFN-␥, tumor necrosis factor alpha (TNF-␣), IL-2, and proinflammatory IL-6, particularly in patients with HAM/TSP (77,78). CX3CR1 is the receptor for fractalkine and is highly expressed on CD16 ϩ cells, which migrate in response to fractalkine, which is known to induce high levels of transendothelial migration of CD16 ϩ monocytes (50).…”

Section: Discussionmentioning

confidence: 99%

Human T Cell Leukemia Virus Type 1 Infection of the Three Monocyte Subsets Contributes to Viral Burden in Humans

Castro-Amarante

Pise-Masison

McKinnon

et al. 2016

J Virol

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A pproximately 2 to 3% of human T cell leukemia virus type 1 (HTLV-1)-infected individuals develop adult T-cell leukemia/lymphoma (ATL) and another 2 to 3% develop HTLV-1-associated myelopathy (HAM)/tropical spastic paraparesis (TSP) in their lifetimes (1-4). In addition to HAM/TSP (5, 6), HTLV-1 is also associated with other inflammatory conditions, such as uveitis (6) Sjögren's syndrome (7), bronchoalveolitis and arthritis (8), and polymyositis (9). It is noteworthy that some patients present with more than one of these inflammatory conditions (10). HTLV-1 primarily infects CD4 ϩ and CD8 ϩ effector and memory T cells and regulatory CD4 ϩ CD25 ϩ T cells (11,12). A high viral DNA burden in peripheral blood mononuclear cells (PBMCs) is a risk factor for HAM/TSP (13) and ATL development (14-16), and patients with HAM/TSP have a higher virus level in the cerebrospinal fluid (CSF) than in the peripheral blood (12). The virus level alone is not sufficient to differentiate symptomatic patients from healthy carriers, suggesting the importance of other factors, including the host immune response (16)(17)(18)(19)(20). HAM/TSP patients present diverse immunological alterations, such as increased levels of spontaneous lymphocyte proliferation (21, 22), tax-specific cytotoxic CD8 ϩ T cell expansion, and the production of high levels of inflammatory cytokines (23)(24)(25). Several studies have also suggested that monocytes are involved in immune reg-

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“…In HAM/TSP, a proinflammatory microenvironment is the hallmark of the immunological profile (31). The cytokine pattern in the peripheral blood from HTVL-1-infected individuals has been evaluated by using in vitro short-term leukocyte incubation and was shown to present distinct clinical grades.…”

Section: Immunopathogenesismentioning

confidence: 99%

“…Thus, HAM/TSP is considered an inflammatory disease in which cellular damage leads to demyelination (3,31). Early in the disease, leptomeninges, blood vessels, and parenchyma are infiltrated by CD4 ϩ and CD8 lymphocytes, B lymphocytes, and foamy macrophages.…”

Section: Htlv-1-associated Myelopathy/tropical Spastic Paraparesismentioning

confidence: 99%

Epidemiology, Treatment, and Prevention of Human T-Cell Leukemia Virus Type 1-Associated Diseases

Gonçalves

Proietti

Ribas³

et al. 2010

Clin Microbiol Rev

407

321

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SUMMARYHuman T-cell leukemia virus type 1 (HTLV-1), the first human retrovirus to be discovered, is present in diverse regions of the world, where its infection is usually neglected in health care settings and by public health authorities. Since it is usually asymptomatic in the beginning of the infection and disease typically manifests later in life, silent transmission occurs, which is associated with sexual relations, breastfeeding, and blood transfusions. There are no prospects of vaccines, and screening of blood banks and in prenatal care settings is not universal. Therefore, its transmission is active in many areas such as parts of Africa, South and Central America, the Caribbean region, Asia, and Melanesia. It causes serious diseases in humans, including adult T-cell leukemia/lymphoma (ATL) and an incapacitating neurological disease (HTLV-associated myelopathy/tropical spastic paraparesis [HAM/TSP]) besides other afflictions such as uveitis, rheumatic syndromes, and predisposition to helminthic and bacterial infections, among others. These diseases are not curable as yet, and current treatments as well as new perspectives are discussed in the present review.

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HTLV-1-Associated Myelopathy/Tropical Spastic Paraparesis (HAM/TSP) Inflammatory Network

Cited by 52 publications

References 103 publications

CD4+ T cell subsets and Tax expression in HTLV-1 associated diseases

CD4+ T cell subsets and Tax expression in HTLV-1 associated diseases

Human T Cell Leukemia Virus Type 1 Infection of the Three Monocyte Subsets Contributes to Viral Burden in Humans

Epidemiology, Treatment, and Prevention of Human T-Cell Leukemia Virus Type 1-Associated Diseases

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