scholarly journals Immunoprofiling of fresh HAM/TSP blood samples show altered innate cell responsiveness

2021 ◽  
Vol 15 (11) ◽  
pp. e0009940
Author(s):  
Brenda Rocamonde ◽  
Nicolas Futsch ◽  
Noemia Orii ◽  
Omran Allatif ◽  
Augusto Cesar Penalva de Oliveira ◽  
...  
Keyword(s):  
Immune Cell ◽  
Leukemia Virus ◽  
Spastic Paraparesis ◽  
Disease Manifestation ◽  
Blood Samples ◽  
Asymptomatic Carriers ◽  
Cell Functions ◽  
Human T Cell ◽  
Disease Occurrence ◽  
T Cell Leukemia Virus

The Human T-cell Leukemia Virus-1 (HTLV-1)-Associated Myelopathy/Tropical Spastic Paraparesis (HAM/TSP) is a devastating neurodegenerative disease with no effective treatment, which affects an increasing number of people in Brazil. Immune cell from the adaptive compartment are involved in disease manifestation but whether innate cell functions participate in disease occurrence has not been evaluated. In this study, we analyzed innate cell responses at steady state and after blood cell stimulation using an agonist of the toll-like receptor (TLR)7/8-signaling pathway in blood samples from HTLV-1-infected volunteers, including asymptomatic carriers and HAM/TSP patients. We observed a lower response of IFNα+ DCs and monocytes in HAM/TSP compared to asymptomatic carriers, as a potential consequence of corticosteroid treatments. In contrast, a higher frequency of monocytes producing MIP-1α and pDC producing IL-12 was detected in HAM/TSP blood samples, together with higher IFNγ responsiveness of NK cells, suggesting an increase sensitivity to inflammatory response in HAM/TSP patients compared to asymptomatic carriers. This sustained inflammatory responsiveness could be linked or be at the origin of the neuroinflammatory status in HAM/TSP patients. Therefore, the mechanism underlying this dysregulations could shed light onto the origins of HAM/TSP disease.

scholarly journals Immunoprofiling of HTLV-1-infected individuals shows altered innate cell responsiveness in HAM/TSP patients.

2021 ◽  
Author(s):  
Brenda Rocamonde ◽  
Nicolas Fustch ◽  
Noemia Orii ◽  
Omran Allatif ◽  
Augusto Cesar Penalva de Oliveira ◽  
...  
Keyword(s):  
Innate Immunity ◽  
Steady State ◽  
Leukemia Virus ◽  
Spastic Paraparesis ◽  
Toll Like Receptor ◽  
Cell Leukemia ◽  
Blood Samples ◽  
Human T Cell ◽  
Disease Occurrence ◽  
T Cell Leukemia Virus

The Human T-cell Leukemia Virus-1 (HTLV-1)-Associated Myelopathy/Tropical Spastic Paraparesis (HAM/TSP) is a devastating neurodegenerative disease with no effective treatment, which affects an increasing number of people in Brazil. A biological blood factor allowing the prediction of the disease occurrence is so far not available. In this study, we analyzed innate immunity responses at steady state and after blood cell stimulation using an agonist of the toll-like receptor (TLR)7/8-signaling pathway in blood samples from HTLV-1-infected volunteers, including asymptomatic carriers and HAM/TSP patients. We observed a lower responsiveness in dendritic cells to produce IFNα. Moreover, we found higher production of IL-12 and Mip-1α by monocytes together with higher levels of IFNγ produced by Natural Killer cells. These deregulations could represent a signature for progression towards HAM/TSP.

scholarly journals Enhanced MDR1 Gene Expression in Human T-Cell Leukemia Virus-I–Infected Patients Offers New Prospects for Therapy

Blood ◽  
1998 ◽  
Vol 91 (7) ◽  
pp. 2467-2474 ◽  
Author(s):  
Alan Lau ◽  
Simon Nightingale ◽  
Graham P. Taylor ◽  
Timothy W. Gant ◽  
Alan J. Cann
Keyword(s):  
Drug Resistance ◽  
T Cell ◽  
Multiple Drug Resistance ◽  
Leukemia Virus ◽  
Spastic Paraparesis ◽  
Leukemic Cells ◽  
T Cell Leukemia ◽  
Cell Leukemia ◽  
Human T Cell ◽  
T Cell Leukemia Virus

Overexpression of P-glycoprotein (P-gp), the protein product of the multidrug resistance gene (MDR1), confers a drug resistant phenotype on cells. This phenotype is reminiscent of human T-cell leukemia virus (HTLV)-transformed leukemic cells, for which no consistently effective chemotherapeutic regime has been found. The presence of an active multiple drug resistance (MDR) phenotype in freshly isolated peripheral blood mononuclear cells (PBMC) from HTLV-I–infected subjects was investigated. Significant P-gp–mediated efflux activity and enhanced MDR1 mRNA expression was observed in nine of 10 HTLV-infected subjects. The development of MDR phenotypes was found to be independent of disease type or status with significant MDR activities being observed in adult T-cell leukemia (ATL), HTLV-associated myelopathy (HAM)/tropical spastic paraparesis (TSP), and asymptomatic HTLV-infected individuals. P-gp–mediated drug efflux was also found to be restricted to CD3+ T-cell populations. Furthermore, we show the novel finding that theMDR1 gene promoter is transcriptionally activated by the HTLV-I tax protein, suggesting a molecular basis for the development of drug resistance in HTLV-I infections. These observations open up the possibility of new chemotherapeutic approaches to HTLV-associated diseases through the use of P-gp inhibitors.

scholarly journals Molecular characterization of human T-cell leukemia virus type 1 gp46 glycoprotein from healthy carriers and tropical spastic paraparesis/HTLV-associated myelopathy infected individuals

Retrovirology ◽  
2014 ◽  
Vol 11 (Suppl 1) ◽  
pp. P83
Author(s):  
Aline CA Mota-Miranda ◽  
Fernanda K Barreto ◽  
Maria FC Amarante ◽  
Everton Baptista ◽  
Joana P Monteiro-Cunha ◽  
...  
Keyword(s):  
T Cell ◽  
Leukemia Virus ◽  
Spastic Paraparesis ◽  
Cell Leukemia ◽  
Cell Leukemia Virus Type ◽  
Human T Cell ◽  
T Cell Leukemia Virus ◽  
Healthy Carriers

scholarly journals Immunopathogenesis and Cellular Interactions in Human T-Cell Leukemia Virus Type 1 Associated Myelopathy/Tropical Spastic Paraparesis

2020 ◽  
Vol 11 ◽  
Author(s):  
Sepehr Aghajanian ◽  
Majid Teymoori-Rad ◽  
Ghazale Molaverdi ◽  
Sayed-Hamidreza Mozhgani
Keyword(s):  
Leukemia Virus ◽  
Spastic Paraparesis ◽  
Tropical Spastic Paraparesis ◽  
Cellular Interactions ◽  
Limb Weakness ◽  
Cell Leukemia Virus Type ◽  
T Lymphotropic Virus ◽  
Human T Cell ◽  
T Cell Leukemia Virus ◽  
Sensory Disturbances

HTLV-1-Associated Myelopathy/Tropical Spastic Paraparesis (HAM/TSP) is a neuropathological disorder in 1–3% of individuals infected with Human T-lymphotropic virus 1 (HTLV-1). This condition is characterized by progressive spastic lower limb weakness and paralysis, lower back pain, bladder incontinence, and mild sensory disturbances resembling spinal forms of multiple sclerosis. This disease also causes chronic disability and is therefore associated with high health burden in areas where HTLV-1 infection is endemic. Despite various efforts in understanding the virus and discovery of novel diagnostic markers, and cellular and viral interactions, HAM/TSP management is still unsatisfactory and mainly focused on symptomatic alleviation, and it hasn’t been explained why only a minority of the virus carriers develop HAM/TSP. This comprehensive review focuses on host and viral factors in association with immunopathology of the disease in hope of providing new insights for drug therapies or other forms of intervention.

scholarly journals Immunopathogenesis of Human T-Cell Leukemia Virus Type-1-Associated Myelopathy/Tropical Spastic Paraparesis: Recent Perspectives

2012 ◽  
Vol 2012 ◽  
pp. 1-12 ◽  
Author(s):  
Mineki Saito ◽  
Charles R. M. Bangham
Keyword(s):  
T Cell ◽  
Virus Type ◽  
Leukemia Virus ◽  
Spastic Paraparesis ◽  
T Cell Leukemia ◽  
Cell Leukemia ◽  
Cell Leukemia Virus Type ◽  
Human T Cell ◽  
T Cell Leukemia Virus

Human T-cell leukemia virus type-1 (HTLV-1) is a replication-competent human retrovirus associated with two distinct types of disease only in a minority of infected individuals: the malignancy known as adult T-cell leukemia (ATL) and a chronic inflammatory central nervous system disease HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). HAM/TSP is a chronic progressive myelopathy characterized by spastic paraparesis, sphincter dysfunction, and mild sensory disturbance in the lower extremities. Although the factors that cause these different manifestations of HTLV-1 infection are not fully understood, accumulating evidence from host population genetics, viral genetics, DNA expression microarrays, and assays of lymphocyte function suggests that complex virus-host interactions and the host immune response play an important role in the pathogenesis of HAM/TSP. Especially, the efficiency of an individual's cytotoxic T-cell (CTL) response to HTLV-1 limits the HTLV-1 proviral load and the risk of HAM/TSP. This paper focuses on the recent advances in HAM/TSP research with the aim to identify the precise mechanisms of disease, in order to develop effective treatment and prevention.

scholarly journals Progressive Spastic Paraparesis Associated with Human T-Cell Leukemia Virus Type I(HTLV-I).

1992 ◽  
Vol 31 (11) ◽  
pp. 1257-1261 ◽  
Author(s):  
Luis CARTIER ◽  
Fernando ARAYA ◽  
Jose Luis CASTILLO ◽  
Fernando RUIZ ◽  
Adriana GORMAZ ◽  
...  
Keyword(s):  
T Cell ◽  
Virus Type ◽  
Leukemia Virus ◽  
Spastic Paraparesis ◽  
Type I ◽  
T Cell Leukemia ◽  
Cell Leukemia ◽  
Cell Leukemia Virus Type ◽  
Human T Cell ◽  
T Cell Leukemia Virus
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