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.

scholarly journals Antigen-Specific T-Cell Responses of Leprosy Patients

2008 ◽  
Vol 15 (11) ◽  
pp. 1659-1665 ◽  
Author(s):  
Malcolm S. Duthie ◽  
Wakako Goto ◽  
Greg C. Ireton ◽  
Stephen T. Reece ◽  
Lucas H. Sampaio ◽  
...  
Keyword(s):  
T Cell ◽  
Mononuclear Cells ◽  
Significant Proportion ◽  
T Cell Responses ◽  
Potential Candidate ◽  
Peripheral Blood Mononuclear ◽  
Cell Responses ◽  
Human T Cell ◽  
Leprosy Patients ◽  
Ifn Γ

ABSTRACT The identification of human T-cell antigens of Mycobacterium leprae could improve treatment and help to disrupt the transmission of leprosy by directing diagnosis and vaccine programs. This study screened a panel of M. leprae recombinant proteins for T-cell recall responses, measured by gamma interferon (IFN-γ) production, among leprosy patients. After initial studies using peripheral blood mononuclear cells from leprosy patients, we transitioned our studies to simple whole-blood assays (WBA), which are more applicable in field or clinical settings. T-cell responses generated in WBA using blood from individuals in Goiânia, Brazil, demonstrated that several M. leprae antigens (ML0276, ML0840, ML1623, ML2044, and 46f) elicited >0.5 IU/ml IFN-γ, and these proteins were classified as immunogenic and leprosy specific. Several of these individual antigens were recognized by cells from >60% of Brazilian paucibacillary (PB) leprosy patients, and ML0276, ML0840, ML1623, and 46f complemented each other such that 82% of PB patients had strong (>1.25 IU/ml IFN-γ) responses to at least one of these proteins. These proteins were also recognized by cells from a significant proportion of the household contacts of multibacillary leprosy patients, but in contrast, few responses were observed in active tuberculosis patients or healthy control groups from areas of endemicity. Our results indicate several potential candidate antigens which may be useful for either leprosy diagnosis or vaccination and demonstrate the utility of leprosy WBA that can be applied broadly in clinical or field settings.

scholarly journals Differential Live Mycobacterium tuberculosis-, M. bovis BCG-, Recombinant ESAT6-, and Culture Filtrate Protein 10-Induced Immunity in Tuberculosis

2009 ◽  
Vol 16 (7) ◽  
pp. 991-998 ◽  
Author(s):  
Zahra Hasan ◽  
Bushra Jamil ◽  
Mussarat Ashraf ◽  
Muniba Islam ◽  
Maqboola Dojki ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Culture Filtrate ◽  
Mononuclear Cells ◽  
Interleukin 10 ◽  
Peripheral Blood Mononuclear ◽  
High Prevalence ◽  
Ifn Γ ◽  
Mycobacterial Antigens ◽  
Induced Immunity ◽  
Culture Filtrate Protein

ABSTRACT The high prevalence of Mycobacterium tuberculosis makes it imperative that immune responses to evaluate could be predictive of infection. We investigated live Mycobacterium- and recombinant antigen-induced cytokine and chemokine responses in patients with active tuberculosis (TB) compared with those of healthy controls from an area where TB is endemic (ECs). M. tuberculosis-, M. bovis BCG-, ESAT6-, and culture filtrate protein 10 (CFP10)-induced responses were determined in peripheral blood mononuclear cells from patients with pulmonary TB (n = 38) and ECs (n = 39). The levels of the cytokines gamma interferon (IFN-γ) and interleukin-10 (IL-10) and the chemokines CCL2, CCL3, and CXCL9 were measured. The levels of M. tuberculosis- and BCG-induced IFN-γ secretion were significantly reduced (P = 0.002 and P < 0.01, respectively), while the amount of IL-10 induced by both virulent (P < 0.01) and avirulent (P = 0.002) mycobacteria was increased in patients with TB. The ESAT6-induced IFN-γ responses were increased in the patients with TB (P = 0.013) compared with those in the EC group. When tuberculin skin test (TST)-negative (TST−; induration, <10 mm) and TST-positive (TST+) donors were studied separately, both TST− and TST+ individuals showed increased IFN-γ responses to M. tuberculosis compared with the responses of the patients with TB (P = 0.037 and P = 0.006, respectively). However, only TST+ ECs showed reduced IFN-γ responses to ESAT6 (P = 0.008) compared with the responses of the patients with TB. The levels of M. tuberculosis-induced CCL2 (P = 0.006) and CXCL9 (P = 0.017) were greater in the patients with TB. The levels of CCL3 secretion in response to Mycobacterium and antigen stimulation were comparable between the two groups. While the levels of ESAT6-induced chemokines did not differ between the patients with TB and the ECs, the levels of CFP10-induced CCL2 (P = 0.01) and CXCL9 (P = 0.001) were increased in the patients. These data indicate differential host IFN-γ, CXCL9, and CCL2 responses to live mycobacteria and mycobacterial antigens and have implications for the identification of potential biomarkers of infection which could be used for the diagnosis of TB.

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.

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