Phenotypic and functional changes in gamma delta T lymphocytes from HTLV-1 carriers

Albuquerque, Raquel Cavalcanti de; Granato, Alessandra; Castro, Isabela Silva de; Torres, Rafael Carvalho; Souza, Flávia Santos; Lima, Marco Antônio; Leite, Ana Cláudia Celestino Bezerra; Espíndola, Otávio de Melo; Echevarria-Lima, Juliana

doi:10.1002/jlb.ma1118-467r

Cited by 6 publications

(3 citation statements)

References 68 publications

(116 reference statements)

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“…DNA was extracted from PBMCs and CSF cells with the QIAamp DNA blood mini kit (Qiagen, Germany), following the manufacturer’s instructions, and HTLV-1 PVL was determined as previously described ( 45 ). Briefly, quantitative PCR was carried out with the Rotor-Gene Probe PCR kit (Qiagen, Germany) in a Rotor-Gene Q 5-plex instrument (Qiagen, Germany).…”

Section: Methodsmentioning

confidence: 99%

Following the Clues: Usefulness of Biomarkers of Neuroinflammation and Neurodegeneration in the Investigation of HTLV-1-Associated Myelopathy Progression

et al. 2021

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Human T-lymphotropic virus type 1 (HTLV-1)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is a neurodegenerative disease due to axonal damage of the corticospinal secondary to an inflammatory response against infected T-cells. In the present work, we aimed to evaluate biomarkers of neurodegeneration and neuroinflammation in the definition of HAM/TSP prognosis. Neurofilament light (NfL) and phosphorylated heavy (pNfH) chains, total Tau protein, cellular prion protein (PrPc), inflammatory chemokines, and neopterin were quantified in paired cerebrospinal fluid (CSF) and serum samples from HAM/TSP patients (n=21), HTLV-1 asymptomatic carriers (AC) (n=13), and HTLV-1 seronegative individuals with non-inflammatory non-degenerative neurological disease (normal-pressure hydrocephalus) (n=9) as a control group. HTLV-1 proviral load in peripheral blood mononuclear cells and the expression of chemokine receptors CCR4, CCR5, and CXCR3 in infected CD4+ T-cells (HTLV-1 Tax+ cells) were also assessed. CSF levels of Tau, NfL, and pNfH were similar between groups, but PrPc and neopterin were elevated in HAM/TSP patients. Most individuals in the control group and all HTLV-1 AC had CSF/serum neopterin ratio < 1.0, and two-thirds of HAM/TSP patients had ratio values > 1.0, which positively correlated with the speed of disease progression and pNfH levels, indicating active neuroinflammation. HAM/TSP patients showed high serum levels of CXCR3-binding chemokines (CXCL9, CXCL10, and CXCL11) and elevated CSF levels of CCL2, CCL3, CCL4, CCL17, CXCL5, CXCL10, and CXCL11. Indeed, CXCL10 concentration in CSF of HAM/TSP patients was 5.8-fold and 8.7-fold higher in than in HTLV-1 AC and controls, respectively, and correlated with CSF cell counts. HAM/TSP patients with typical/rapid disease progression had CSF/serum CXCL10 ratio > 1.0 and a higher frequency of CXCR3+Tax+CD4+ T-cells in blood, which indicated a positive gradient for the migration of infected cells and infiltration into the central nervous system. In conclusion, the slow progression of HAM/TSP abrogates the usefulness of biomarkers of neuronal injury for the disease prognosis. Thus, markers of inflammation provide stronger evidence for HAM/TSP progression, particularly the CSF/serum neopterin ratio, which may contribute to overcome differences between laboratory assays.

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Section: Methodsmentioning

confidence: 99%

Following the Clues: Usefulness of Biomarkers of Neuroinflammation and Neurodegeneration in the Investigation of HTLV-1-Associated Myelopathy Progression

et al. 2021

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“…( 31 ), and with a report that also found diminished Vγ9Vδ2 T cells in HAM/TSP patients ( 32 ). Contrarily, another publication did not report an alteration of the Vγ9Vδ2 T cells in HTLV-1 infected patients but described changes in the phenotype and function of γδ T cells ( 33 ). This discrepancy could be due to the fact that in our study, patients with autoimmune or inflammatory diseases or other co-infections were excluded as they could also alter the percentage of different T cell populations as is the case for lymphomatic malignancies ( 34 ).…”

Section: Discussionmentioning

confidence: 99%

Phenotypic and functional analysis of γδ T cells in the pathogenesis of human T-cell lymphotropic virus type 1 infection

Ruggieri

Ducasa²,

Juraske³

et al. 2022

Front. Immunol.

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The human T-cell leukemia virus type 1 (HTLV-1) is the cause of serious malignant and inflammatory diseases, including adult T-cell leukemia and lymphoma and tropical spastic paraparesis. The potential protective role of γδ T cells in HTLV-1 infection remains unclear. Here, demonstrate that there is a decrease in the amount of Vγ9Vδ2 T cells in patients with HTLV-1, especially in those with HTLV-1 associated pathologies. This suggests that γδ T cells could be involved in controlling the virus. Indeed, we found that Vγ9Vδ2 T cells, expanded from non-infected individuals, can kill cells expressing the viral proteins HBZ and Tax and this phenotype is reversed in the presence of mevastatin. Cytotoxicity by Vγ9Vδ2 T cells was not associated with an increase of INF-γ production. In sharp contrast, killing by NK cells was reduced by Tax expression. Thus, our study provides initial evidence for a potential protective role of Vγ9Vδ2 T cells against HTLV-1 infection. Therapeutic exploitation of these insights is feasible with current technologies of T-cell therapies and could provide novel tools to prevent and treat HTLV-1-associated malignancies and neurologic complications.

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“…γδ T cells are a subset of T lymphocytes that are classified as CD3 and T cell receptor (TCR) γδ double positive [1,2]. γδ T cells occupy 5-10 percentage of peripheral T cells, while γδ T cells can be as high as 50% of total CD3 + T cells in some mucosal tissues [3,4].…”

Section: Introductionmentioning

confidence: 99%

Long noncoding RNA TANCR promotes γδ T cells activation by regulating TRAIL expression in cis

et al. 2020

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Background: γδ T cells are an important subset of T lymphocytes that play important roles in innate and adaptive immunity via the secretion of various cytokines. Previous studies have found that long noncoding RNAs (lncRNAs) are critical regulators that contribute to the development of immune cells. However, the functions of lncRNAs in the γδ T cells remains poorly studied. Results: Here, we identified the novel function of lncRNA NONHSAT196558.1 in isopentenyl pyrophosphate (IPP)activated and-expanded γδ T cells using RNA-seq. As it functioned as an activating noncoding RNA of tumor necrosis factor related apoptosis-inducing ligand (TRAIL), an important cytotoxic cytokine that expressed by γδ T cells in responding to various infectious agents, we named this lncRNA as TANCR. Secondly, the expression of TANCR was found to be positively correlated with TRAIL expression in IPP activated γδ T cells. In addition, TANCR was confirmed to localized both in nucleus and cytoplasm. Finally, a loss-of-function was conducted by using siRNA/ASO or CRISPR/ Cas9 system to knockdown or knockout TANCR, and confirmed that silencing of TANCR inhibits TRAIL expression in several kinds of cells, including HEK293T cells, Jurkat cells, and primary γδ T cells. Conclusion: These evidences demonstrate that TANCR play important roles in γδ T cell activation. Furthermore, TANCR may be involved in the cytotoxicity of γδ T cells. This study aims to further our understanding of the molecular mechanisms underlying lncRNA-mediated immune responses.

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Phenotypic and functional changes in gamma delta T lymphocytes from HTLV-1 carriers

Cited by 6 publications

References 68 publications

Following the Clues: Usefulness of Biomarkers of Neuroinflammation and Neurodegeneration in the Investigation of HTLV-1-Associated Myelopathy Progression

Following the Clues: Usefulness of Biomarkers of Neuroinflammation and Neurodegeneration in the Investigation of HTLV-1-Associated Myelopathy Progression

Phenotypic and functional analysis of γδ T cells in the pathogenesis of human T-cell lymphotropic virus type 1 infection

Long noncoding RNA TANCR promotes γδ T cells activation by regulating TRAIL expression in cis

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