The roles of acquired and innate immunity in human T-cell leukemia virus type 1-mediated diseases

Kannagi, Mari; Hasegawa, Atsuhiko; Takamori, Ayako; Kinpara, Shuichi; Utsunomiya, Atae

doi:10.3389/fmicb.2012.00323

Cited by 26 publications

(26 citation statements)

References 91 publications

(117 reference statements)

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“…This could be due to high proviral loads (Fig. 1) leading to chronic antigen stimulation and T cell exhaustion previously shown for HTLV-1 and other chronic viruses (52–57). We then compared the frequencies of various phenotypically distinct subsets of CD8 + T cells both at basal level as well as upon CEF/SEB/Tax stimulation and did not observe expansion of naïve, effector or memory T cells in any group (Fig.…”

Section: Discussionmentioning

confidence: 86%

Lack of Recall Response to Tax in ATL and HAM/TSP Patients But Not in Asymptomatic Carriers of Human T-cell Leukemia Virus Type 1

et al. 2013

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The immunopathogenic mechanisms responsible for debilitating neurodegenerative and oncologic diseases associated with human T-cell leukemia virus type 1 (HTLV-1) are not fully understood. In this respect, a patient cohort from HTLV-1 endemic region that included seronegative controls (controls), asymptomatic carriers (ACs), and patients with adult T-cell leukemia (ATL) or HTLV-associated myelopathy/tropical spastic paraparesis (HAM/TSP) was analyzed for CD8+ T cells functionality in response to the viral antigen Tax and a superantigen SEB. Overall, there was a poor recall response to Tax and less polyfunctionality in cells from ATL and HAM/TSP patients but not in ACs explaining why these cells remain ineffective in limiting viral burden and controlling disease progression. On the other hand, response to superantigen SEB was similar in all the groups, suggesting that the observed defects in CD8 + T cells are not generalized but rather HTLV-specific. As an underlying mechanism, programmed death-1 (PD-1) receptor was found to be highly unregulated in Tax-responsive cells from ATL and HAM/TSP but not from ACs and directly correlated with the lack of polyfunctionality in these individuals. Further, an opposite dynamic was observed between PD-1 and MIP-1α with proviral loads revealing new avenues of understanding the immunopathogenesis of human chronic viral infections. Additionally, we identified key cytokine signatures defining the immune activation status of clinical samples by the luminex analyses. Collectively, our findings suggest that reconstitution of fully functional CTLs, stimulation of MIP-1α expression, and/or blockade of the PD-1 pathway as potential approaches for immunotherapy and therapeutic vaccine against HTLV-mediated diseases.

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Section: Discussionmentioning

confidence: 86%

Lack of Recall Response to Tax in ATL and HAM/TSP Patients But Not in Asymptomatic Carriers of Human T-cell Leukemia Virus Type 1

et al. 2013

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“…The presence of a lymphocytic infiltrate in CNS lesions suggests that the immune or inflammatory response to HTLV-1 causes the observed tissue damage. The innate immune response has been relatively little studied in HTLV-1 infection, but recent work has revealed the important roles of interferons [72][73][74] . A gene expression microarray study of peripheral blood provided a strong pointer to interferons as a major pathway of pathogenesisthe study revealed a transcriptional signature of interferon-stimulated genes in patients with HAM/TSP 74 .…”

mentioning

confidence: 99%

HTLV-1-associated myelopathy/tropical spastic paraparesis

Bangham

Araújo

Yamano

et al. 2015

Nat Rev Dis Primers

196

225

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Human T-lymphotropic virus 1 (HTLV-1)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is a progressive disease of the CNS that causes weakness or paralysis of the legs, lower back pain and urinary symptoms. HAM/TSP was first described in Jamaica in the nineteenth century, but the aetiology of the condition, infection with the retrovirus HTLV-1, was only identified in the 1980s. HAM/TSP causes chronic disability and, accordingly, imposes a substantial health burden in areas where HTLV-1 infection is endemic. Since the discovery of the cause of HAM/TSP, considerable advances have been made in the understanding of the virology, immunology, cell biology and pathology of HTLV-1 infection and its associated diseases. However, progress has been limited by the lack of accurate animal models of the disease. Moreover, the treatment of HAM/TSP remains highly unsatisfactory: antiretroviral drugs have little impact on the infection and, although potential disease-modifying therapies are widely used, their value is unproved. At present, clinical management is focused on symptomatic treatment and counselling. Here, we summarize current knowledge on the epidemiology, pathogenesis and treatment of HAM/TSP and identify areas in which further research is needed. For an illustrated summary of this Primer, visit: http://go.nature.com/tjZCFM.

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“…Tax is a highly immunogenic protein, and therefore it is a main target of CTL. [33][34][35] In addition, Tax might be involved in the emergence of neoantigens in ATL cells, as it has clastogenic and genotoxic potential. 17,30,36 Thus, Tax evokes a host immune reaction against HTLV-1infected and ATL cells.…”

Section: Htlv-1 Tax and Hbzmentioning

confidence: 99%

Oncogenic spiral by infectious pathogens: Cooperation of multiple factors in cancer development

Yasunaga

Matsuoka

2017

Cancer Science

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Chronic infection is one of the major causes of cancer, and there are several mechanisms for infection‐mediated oncogenesis. Some pathogens encode gene products that behave like oncogenic factors, hijacking cellular pathways to promote the survival and proliferation of infected cells in vivo. Some of these viral oncoproteins trigger a cellular damage defense response leading to senescence; however, other viral factors hinder this suppressive effect, suggesting that cooperation of those viral factors is important for malignant transformation. Coinfection with multiple agents is known to accelerate cancer development in certain cases. For example, parasitic or bacterial infection is a risk factor for adult T‐cell leukemia‐lymphoma induced by human T‐cell leukemia virus type 1, and Epstein‐Barr virus and malaria are closely associated with endemic Burkitt lymphoma. Human immunodeficiency virus type 1 infection is accompanied by various types of infection‐related cancer. These findings indicate that these oncogenic pathogens can cooperate to overcome host barriers against cancer development. In this review, the authors focus on the collaborative strategies of pathogens for oncogenesis from two different points of view: (i) the cooperation of two or more different factors encoded by a single pathogen; and (ii) the acceleration of oncogenesis by coinfection with multiple agents.

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The roles of acquired and innate immunity in human T-cell leukemia virus type 1-mediated diseases

Cited by 26 publications

References 91 publications

Lack of Recall Response to Tax in ATL and HAM/TSP Patients But Not in Asymptomatic Carriers of Human T-cell Leukemia Virus Type 1

Lack of Recall Response to Tax in ATL and HAM/TSP Patients But Not in Asymptomatic Carriers of Human T-cell Leukemia Virus Type 1

HTLV-1-associated myelopathy/tropical spastic paraparesis

Oncogenic spiral by infectious pathogens: Cooperation of multiple factors in cancer development

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