scholarly journals Global expression of noncoding RNome reveals dysregulation of small RNAs in patients with HTLV-1–associated adult T-cell leukemia: a pilot study

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Andrezza Nascimento ◽  
Daniela Raguer Valadão de Souza ◽  
Rodrigo Pessôa ◽  
Anna Julia Pietrobon ◽  
Youko Nukui ◽  
...  
Keyword(s):  
T Cell ◽  
Small Rnas ◽  
Mononuclear Cells ◽  
Transforming Growth Factor ◽  
Illumina Miseq ◽  
Mapk Signaling ◽  
Mitogen Activated Protein Kinase ◽  
Peripheral Blood Mononuclear ◽  
Potential Implication ◽  
Human T Cell

Abstract Background Adult T cell lymphoma/leukemia (ATLL) is a peripheral T-cell neoplasm caused by human T-cell lymphotropic virus-1 (HTLV-1). Small RNAs (sRNAs), including microRNAs (miRNAs), play a pivotal role in the initiation and development of hematological malignancies and may represent potential therapeutic target molecules. However, little is known about how these molecules impact the pathogenesis of ATLL. In this study, we aimed to identify sRNA expression signatures associated with ATLL and to investigate their potential implication in the pathophysiology of the disease. Methods Small-RNAseq analysis was performed in peripheral blood mononuclear cells from HTLV-1- associated ATLL (n = 10) in comparison to asymptomatic carriers (n = 8) and healthy controls (n = 5). Sequencing was carried out using the Illumina MiSeq platform, and the deregulation of selected miRNAs was validated by real-time PCR. Pathway analyses of most deregulated miRNA were performed and their global profiling was combined with transcriptome data in ATLL. Results The sequencing identified specific sRNAs signatures associated with ATLL patients that target pathways relevant in ATLL, such as the transforming growth factor-(βTGF-β), Wnt, p53, apoptosis, and mitogen-activated protein kinase (MAPK) signaling cascades. Network analysis revealed several miRNAs regulating highly connected genes within the ATLL transcriptome. miR-451-3p was the most downregulated miRNA in active patients. Conclusions Our findings shed light on the expression of specific sRNAs in HTLV-1 associated ATLL, which may represent promising candidates as biomarkers that help monitor the disease activity.

scholarly journals Global expression of noncoding RNome reveals dysregulation of small RNAs in patients with HTLV-1–associated adult T-cell leukemia: a pilot study

2021 ◽  
Author(s):  
Andrezza Nacimento ◽  
Daniela Raguer Valadão de Souza ◽  
Rodrigo Pessôa ◽  
Anna Julia Pietrobon ◽  
Youko Nukui ◽  
...  
Keyword(s):  
T Cell ◽  
Small Rnas ◽  
Mononuclear Cells ◽  
Transforming Growth Factor ◽  
Illumina Miseq ◽  
Mapk Signaling ◽  
Mitogen Activated Protein Kinase ◽  
Peripheral Blood Mononuclear ◽  
Potential Implication ◽  
Human T Cell

Abstract Background: Adult T cell lymphoma/leukemia (ATLL) is a peripheral T-cell neoplasm caused by human T-cell lymphotropic virus-1 (HTLV-1). Small RNAs (sRNAs), including microRNAs (miRNAs), play a pivotal role in the initiation and development of hematological malignancies and may represent potential therapeutic target molecules. However, little is known about how these molecules impact the pathogenesis of ATLL. In this study, we aimed to identify sRNA expression signatures associated with ATLL and to investigate their potential implication in the pathophysiology of the disease. Methods: Small-RNAseq analysis was performed in peripheral blood mononuclear cells from HTLV-1- associated ATLL (n = 10) in comparison to asymptomatic carriers (n = 8) and healthy controls (n = 5). Sequencing was carried out using the Illumina MiSeq platform, and the deregulation of selected miRNAs was validated by real-time PCR. Pathway analyses of most deregulated miRNA were performed and their global profiling was combined with transcriptome data in ATLL. Results: The sequencing identified specific sRNAs signatures associated with ATLL patients that target pathways relevant in ATLL, such as the transforming growth factor-(βTGF-β), Wnt, p53, apoptosis, and mitogen-activated protein kinase (MAPK) signaling cascades. Network analysis revealed several miRNAs regulating highly connected genes within the ATLL transcriptome. miR-451-3p was the most downregulated miRNA in active patients. Conclusions: Our findings shed light on the expression of specific sRNAs in HTLV-1 associated ATLL, which may represent promising candidates as biomarkers that help monitor the disease activity.

scholarly journals Global expression of noncoding RNome reveals dysregulation of small RNAs in patients with HTLV-1–associated adult T-cell leukemia: a pilot study

2020 ◽  
Author(s):  
Andrezza Nacimento ◽  
Daniela Raguer Valadão de Souza ◽  
Rodrigo Pessôa ◽  
Anna Julia Pietrobon ◽  
Youko Nukui ◽  
...  
Keyword(s):  
T Cell ◽  
Small Rnas ◽  
Mononuclear Cells ◽  
Illumina Miseq ◽  
Mapk Signaling ◽  
Peripheral Blood Mononuclear ◽  
Potential Implication ◽  
Adult T Cell Leukemia ◽  
Human T Cell ◽  
Pathway Analyses

Abstract Background Adult T cell lymphoma/leukemia (ATLL) is a peripheral T-cell neoplasm caused by human T-cell lymphotropic virus-1 (HTLV-1). Small RNAs (sRNAs), including microRNAs (miRNAs), play a pivotal role in the initiation and development of hematological malignancies and may represent potential therapeutic target molecules. However, little is known about how these molecules impact on the pathogenesis of ATLL. In this study, we aimed to identify sRNA expression signatures associated with ATLL and to investigate their potential implication in the pathophysiology of the disease. Methods Small-RNAseq analysis was performed in peripheral blood mononuclear cells from HTLV-1- associated ATLL (n = 10) in comparison to asymptomatic carriers (n = 8) and healthy controls (n = 5). Sequencing was carried out using the Illumina MiSeq platform, and the deregulation of selected miRNAs was validated by real-time PCR. Pathway analyses of most deregulated miRNA were performed and their global profiling was combined with transcriptome data in ATLL. Results The sequencing identified specific sRNAs signatures associated with ATLL patients that target pathways relevant in ATLL, such as TGF-β, Wnt, p53, apoptosis, and MAPK signaling cascades. Network analysis revealed several miRNAs regulating highly connected genes within the ATLL transcriptome. miR-451-3p was the most downregulated miRNA in active patients. Conclusions Our findings shed light on the expression of specific sRNAs in HTLV-1 associated ATLL, which may represent promising candidates as biomarkers that help monitor the disease activity.

scholarly journals Antigenic Equivalence of Human T-Cell Responses toMycobacterium tuberculosis-Specific RD1-Encoded Protein Antigens ESAT-6 and Culture Filtrate Protein 10 and to Mixtures of Synthetic Peptides

2000 ◽  
Vol 68 (6) ◽  
pp. 3314-3321 ◽  
Author(s):  
Sandra M. Arend ◽  
Annemieke Geluk ◽  
Krista E. van Meijgaarden ◽  
Jaap T. van Dissel ◽  
Michael Theisen ◽  
...  
Keyword(s):  
T Cell ◽  
Culture Filtrate ◽  
Large Scale ◽  
Mononuclear Cells ◽  
Genomic Region ◽  
Protein Antigens ◽  
Peripheral Blood Mononuclear ◽  
Human T Cell ◽  
Peptide Mixtures ◽  
Culture Filtrate Protein

ABSTRACT The early secreted antigenic target 6-kDa protein (ESAT-6) and culture filtrate protein 10 (CFP-10) are promising antigens for reliable immunodiagnosis of tuberculosis. Both antigens are encoded by RD1, a genomic region present in all strains of Mycobacterium tuberculosis and M. bovis but lacking in all M. bovis bacillus Calmette-Guérin vaccine strains. Production and purification of recombinant antigens are laborious and costly, precluding rapid and large-scale testing. Aiming to develop alternative diagnostic reagents, we have investigated whether recombinant ESAT-6 (rESAT-6) and recombinant CFP-10 (rCFP-10) can be replaced with corresponding mixtures of overlapping peptides spanning the complete amino acid sequence of each antigen. Proliferation of M. tuberculosis-specific human T-cell lines in response to rESAT-6 and rCFP-10 and that in response to the corresponding peptide mixtures were almost completely correlated (r = 0.96,P < 0.0001 for ESAT-6; r = 0.98,P < 0.0001 for CFP-10). More importantly, the same was found when gamma interferon production by peripheral blood mononuclear cells in response to these stimuli was analyzed (r = 0.89, P < 0.0001 for ESAT-6;r = 0.89, P < 0.0001 for CFP-10). Whole protein antigens and the peptide mixtures resulted in identical sensitivity and specificity for detection of infection with M. tuberculosis. The peptides in each mixture contributing to the overall response varied between individuals with different HLA-DR types. Interestingly, responses to CFP-10 were significantly higher in the presence of HLA-DR15, which is the major subtype of DR2. These results show that mixtures of synthetic overlapping peptides have potency equivalent to that of whole ESAT-6 and CFP-10 for sensitive and specific detection of infection with M. tuberculosis, and peptides have the advantage of faster production at lower cost.

scholarly journals Effect of Lamivudine on Transmission of Human T-Cell Lymphotropic Virus Type 1 to Adult Peripheral Blood Mononuclear Cells In Vitro

2002 ◽  
Vol 46 (9) ◽  
pp. 3080-3083 ◽  
Author(s):  
Emanuela Balestrieri ◽  
Giancarlo Forte ◽  
Claudia Matteucci ◽  
Antonio Mastino ◽  
Beatrice Macchi
Keyword(s):  
T Cell ◽  
Virus Type ◽  
Peripheral Blood Mononuclear Cells ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Peripheral Blood Mononuclear ◽  
Human T Cell ◽  
Blood Mononuclear Cells

ABSTRACT The effects of lamivudine (3TC) on in vitro infection of peripheral blood mononuclear cells (PBMC) from healthy donors with human T-cell lymphotropic virus type 1 (HTLV-1) were investigated. Direct measures of viral replication (viral DNA, RNA, and protein) all gave similar, very high 50% inhibitory concentrations in comparison with those previously reported for zidovudine. Nevertheless, 3TC inhibited HTLV-1-driven long-term growth of infected PBMC in vitro at concentrations (6.25 μM) which had poor or no direct antiviral effects, suggesting that another mechanism may be playing a role.

scholarly journals Defective Human T-Cell Lymphotropic Virus Type I (HTLV-I) Provirus in 10 Chilean Seronegative Patients with Tropical Spastic Paraparesis or HTLV-I-Associated Myelopathy

1998 ◽  
Vol 36 (6) ◽  
pp. 1811-1813 ◽  
Author(s):  
Eugenio Ramirez ◽  
Luis Cartier ◽  
Maritza Rios ◽  
Jorge Fernandez
Keyword(s):  
T Cell ◽  
Virus Type ◽  
Peripheral Blood Mononuclear Cells ◽  
Mononuclear Cells ◽  
Spastic Paraparesis ◽  
Tropical Spastic Paraparesis ◽  
Type I ◽  
Peripheral Blood Mononuclear ◽  
Human T Cell ◽  
Blood Mononuclear Cells

We studied the presence of tax and ltrgenes from human T-cell lymphotropic virus type I (HTLV-I) provirus in the peripheral blood mononuclear cells from 15 seronegative patients with tropical spastic paraparesis or HTLV-I-associated myelopathy by PCR. Only a region of the tax gene from 10 patients was amplified. The nucleotide homologies of six Chilean isolates to the ATK-1 clone ranged between 98.7 and 99.4%.

scholarly journals Delineation of an immunoregulatory amplifier population recognizing autologous Ia molecules. Analysis with human T cell clones.

1984 ◽  
Vol 159 (2) ◽  
pp. 559-576 ◽  
Author(s):  
A Bensussan ◽  
S C Meuer ◽  
S F Schlossman ◽  
E L Reinherz
Keyword(s):  
T Cell ◽  
B Cells ◽  
Mononuclear Cells ◽  
Human Peripheral Blood ◽  
Soft Agar ◽  
Peripheral Blood Mononuclear ◽  
Human T Cell ◽  
Cell Clones ◽  
Class Ii Mhc ◽  
Autoreactive Cells

Autoreactive T lymphocytes were generated by culturing human peripheral blood mononuclear cells with an antigen-specific major histocompatibility complex (MHC)-restricted autologous inducer T cell, termed RW17C and subsequently cloned in soft agar. The majority of such clones (AC1-13) expressed the T3+T4+T8-T11+Ia+ phenotype and were directed at autologous class II MHC gene products found on B cells, macrophages, and B lymphoblastoid cells as judged by their proliferative response to the latter. For this recognition, the clones employed a T3-Ti molecular complex and a T4 structure analogous to those found on allospecific T cells. Perhaps more importantly, it was observed that the same AC1-13 autoreactive clones (AC) induced autologous B cells to produce high levels of immunoglobulin in the absence of exogenous antigen and could synergize with the RW17C clone to effect maximal B cell Ig production. These results support the notion that such autoreactive cells can function in a physiologic amplifier role by facilitating induction via an internal set of signals (i.e. autologous MHC).

scholarly journals CD30-mediated signaling promotes the development of human T helper type 2-like T cells.

1995 ◽  
Vol 182 (6) ◽  
pp. 1655-1661 ◽  
Author(s):  
G Del Prete ◽  
M De Carli ◽  
M M D'Elios ◽  
K C Daniel ◽  
F Almerigogna ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
T Cells ◽  
T Cell ◽  
Mononuclear Cells ◽  
Growth Factor Receptor ◽  
Cytokine Secretion ◽  
T Helper ◽  
Peripheral Blood Mononuclear ◽  
Human T Cell

We have recently shown that CD30, a member of the tumor necrosis factor/nerve growth factor receptor superfamily, is preferentially expressed by human T cell clones producing T helper (Th) type 2 cytokines. We report here that costimulation with an agonistic anti-CD30 monoclonal antibody enhanced antigen (Ag)-induced proliferation and cytokine secretion by established human Th2 and Th0 clones. Moreover, costimulation of peripheral blood mononuclear cells with the same anti-CD30 monoclonal antibody resulted in the preferential development of Ag-specific T cell lines and clones showing a Th2-like profile of cytokine secretion. In contrast, early blockade in bulk culture of CD30 ligand-CD30 interaction shifted the development of Ag-specific T cells towards the opposite (Th1-like) phenotype. Taken together, these data suggest that CD30 triggering of activated Th cells by CD30 ligand-expressing Ag-presenting cells may represent an important costimulatory signaling for the development of Th2-type responses.

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