scholarly journals Contribution of CD8+ T Cells to Gamma Interferon Production in Human Tuberculosis

2001 ◽  
Vol 69 (5) ◽  
pp. 3497-3501 ◽  
Author(s):  
Homayoun Shams ◽  
Benjamin Wizel ◽  
Stephen E. Weis ◽  
Buka Samten ◽  
Peter F. Barnes
Keyword(s):  
T Cells ◽  
Mononuclear Cells ◽  
Severe Disease ◽  
Clinical Manifestations ◽  
Gamma Interferon ◽  
Interferon Production ◽  
Peripheral Blood Mononuclear ◽  
Tuberculosis Patients ◽  
Ifn Γ ◽  
Stimulation Of

ABSTRACT The proportions of peripheral blood mononuclear cells (PBMC), CD4+ T cells, and CD8+ T cells that produce gamma interferon (IFN-γ) in response to Mycobacterium tuberculosis were markedly reduced in tuberculosis patients, particularly in those with severe disease. Depletion of CD4+ but not CD8+ cells prior to stimulation of PBMC with M. tuberculosis abolished IFN-γ production. These results show that (i) IFN-γ production by CD8+ and CD4+ cells correlates with the clinical manifestations ofM. tuberculosis infection and (ii) IFN-γ production by CD8+ cells depends on CD4+ cells.

scholarly journals Failure of Gamma Interferon but Not Interleukin-10 Expression in Response to Human Papillomavirus Type 11 E6 Protein in Respiratory Papillomatosis

2004 ◽  
Vol 11 (3) ◽  
pp. 538-547 ◽  
Author(s):  
James A. DeVoti ◽  
Bettie M. Steinberg ◽  
David W. Rosenthal ◽  
Lynda Hatam ◽  
Andrea Vambutas ◽  
...  
Keyword(s):  
T Cells ◽  
Human Papillomavirus ◽  
Mononuclear Cells ◽  
Severe Disease ◽  
Interleukin 2 ◽  
Cytokine Expression ◽  
Gamma Interferon ◽  
Peripheral Blood Mononuclear ◽  
Ifn Γ

ABSTRACT Recurrent respiratory papillomatosis (RRP) is a chronic, debilitating disease of the upper airway caused by human papillomavirus type 6 (HPV-6) or HPV-11. We describe responses of peripheral blood mononuclear cells (PBMC) and T cells from RRP patients and controls to the HPV-11 early proteins E6 and E7. PBMC were exposed in vitro to purified E6 or E7 proteins or transduced with fusion proteins containing the first 11 amino acids of the human immunodeficiency virus type 1 protein tat fused to E6 or E7 (tat-E6/tat-E7). TH1-like (interleukin-2 [IL-2], gamma interferon [IFN-γ], IL-12, and IL-18), and TH2-like (IL-4 and IL-10) cytokine mRNAs were identified by reverse transcription-PCR, and IFN-γ and IL-10 cytokine-producing cells were identified by enzyme-linked immunospot assay. These studies show that HPV-11 E6 skews IL-10-IFN-γ expression by patients with RRP toward greater expression of IL-10 than of IFN-γ. In addition, there is a general cytokine hyporesponsiveness to E6 that is more prominent for TH1-like cytokine expression by patients with severe disease. Patients showed persistent IL-10 cytokine expression by the nonadherent fraction of PBMC when challenged with E6 and tat-E6, and, in contrast to controls, both T cells and non-T cells from patients expressed IL-10. However, E7/tat-E7 cytokine responses in patients with RRP were similar to those of the controls. In contrast, E6 inhibited IL-2 and IL-18 mRNA expression that would further contribute to a cytokine microenvironment unfavorable to HPV-specific, T-cell responses that should control persistent HPV infection. In summary, E6 is the dominant inducer of cytokine expression in RRP, and it induces a skewed expression of IL-10 compared to the expression of IFN-γ.

scholarly journals Depressed CD40 Ligand Expression Contributes to Reduced Gamma Interferon Production in Human Tuberculosis

2000 ◽  
Vol 68 (5) ◽  
pp. 3002-3006 ◽  
Author(s):  
Buka Samten ◽  
Elaine K. Thomas ◽  
Jianhua Gong ◽  
Peter F. Barnes
Keyword(s):  
Mononuclear Cells ◽  
Cd40 Ligand ◽  
Gamma Interferon ◽  
Interferon Production ◽  
Peripheral Blood Mononuclear ◽  
Soluble Factors ◽  
Tuberculosis Patients ◽  
Blood Mononuclear Cells ◽  
Ligand Expression ◽  
Ifn Γ

ABSTRACT Expression of CD40 ligand (CD40L) correlated directly withMycobacterium tuberculosis-stimulated gamma interferon (IFN-γ) production by peripheral blood mononuclear cells (PBMC) from tuberculosis patients and healthy tuberculin reactors. The CD40L agonist increased M. tuberculosis-induced IFN-γ production by PBMC, and anti-CD40 or anti-CD40L antibodies reduced IFN-γ production. CD40L expression on PBMC was reduced by exposure to B cells and to soluble factors from M. tuberculosis-infected monocytes. These findings suggest that CD40L dysregulation contributes to reduced IFN-γ production in human tuberculosis.

scholarly journals Neutralization of Interleukin-10 from CD14+ Monocytes Enhances Gamma Interferon Production in Peripheral Blood Mononuclear Cells from Mycobacterium avium subsp. paratuberculosis-Infected Goats

2009 ◽  
Vol 16 (7) ◽  
pp. 1003-1011 ◽  
Author(s):  
Kari R. Lybeck ◽  
Anne K. Storset ◽  
Ingrid Olsen
Keyword(s):  
T Cells ◽  
Mycobacterium Avium ◽  
Mononuclear Cells ◽  
Cell Receptor ◽  
Interleukin 10 ◽  
Gamma Interferon ◽  
Regulatory Mechanisms ◽  
Interferon Production ◽  
Peripheral Blood Mononuclear

ABSTRACT The gamma interferon assay is used to identify Mycobacterium avium subsp. paratuberculosis-infected animals. It has been suggested that regulatory mechanisms could influence the sensitivity of the test when it is performed with cells from cattle and that the neutralization of interleukin-10 (IL-10) in vitro would increase the gamma interferon responses. To investigate the regulatory mechanisms affecting the gamma interferon assay with cells from goats, blood was collected from M. avium subsp. paratuberculosis-infected, M. avium subsp. paratuberculosis-exposed, and noninfected goats. Neutralization of IL-10 by a monoclonal antibody resulted in increased levels of gamma interferon production in M. avium subsp. paratuberculosis purified protein derivative (PPDj)-stimulated samples from both infected and exposed goats. However, the levels of gamma interferon release were also increased in unstimulated cells and in PPDj-stimulated cells from some noninfected animals following neutralization. Depletion of putative regulatory CD25high T cells had no clear effect on the number of gamma-interferon-producing cells. The IL-10-producing cells were identified to be mainly CD14+ major histocompatibility complex class II-positive monocytes in both PPDj-stimulated and control cultures and not regulatory T cells. However, possible regulatory CD4+ CD25+ T cells produced IL-10 in response to concanavalin A stimulation. The numbers of CD4+, CD8+, and CD8+ γδT-cell receptor-positive cells producing gamma interferon increased following IL-10 neutralization. These results provide insight into the source and the role of IL-10 in gamma interferon assays with cells from goats and suggest that IL-10 from monocytes can regulate both innate and adaptive gamma interferon production from several cell types. Although IL-10 neutralization increased the sensitivity of the gamma interferon assay, the specificity of the test could be compromised.

scholarly journals The STAT4 SLE risk allele rs7574865[T] is associated with increased IL-12-induced IFN-γ production in T cells from patients with SLE

2018 ◽  
Vol 77 (7) ◽  
pp. 1070-1077 ◽  
Author(s):  
Niklas Hagberg ◽  
Martin Joelsson ◽  
Dag Leonard ◽  
Sarah Reid ◽  
Maija-Leena Eloranta ◽  
...  
Keyword(s):  
T Cells ◽  
Immune Cells ◽  
Lupus Erythematosus ◽  
Kinase Inhibitors ◽  
Mononuclear Cells ◽  
Risk Allele ◽  
Severe Disease ◽  
Janus Kinase ◽  
Peripheral Blood Mononuclear ◽  
Ifn Γ

ObjectivesGenetic variants in the transcription factor STAT4 are associated with increased susceptibility to systemic lupus erythematosus (SLE) and a more severe disease phenotype. This study aimed to clarify how the SLE-associated intronic STAT4 risk allele rs7574865[T] affects the function of immune cells in SLE.MethodsPeripheral blood mononuclear cells (PBMCs) were isolated from 52 genotyped patients with SLE. Phosphorylation of STAT4 (pSTAT4) and STAT1 (pSTAT1) in response to interferon (IFN)-α, IFN-γ or interleukin (IL)-12, total levels of STAT4, STAT1 and T-bet, and frequency of IFN-γ+ cells on IL-12 stimulation were determined by flow cytometry in subsets of immune cells before and after preactivation of cells with phytohaemagglutinin (PHA) and IL-2. Cellular responses and phenotypes were correlated to STAT4 risk allele carriership. Janus kinase inhibitors (JAKi) selective for TYK2 (TYK2i) or JAK2 (JAK2i) were evaluated for inhibition of IL-12 or IFN-γ-induced activation of SLE PBMCs.ResultsIn resting PBMCs, the STAT4 risk allele was neither associated with total levels of STAT4 or STAT1, nor cytokine-induced pSTAT4 or pSTAT1. Following PHA/IL-2 activation, CD8+ T cells from STAT4 risk allele carriers displayed increased levels of STAT4 resulting in increased pSTAT4 in response to IL-12 and IFN-α, and an augmented IL-12-induced IFN-γ production in CD8+ and CD4+ T cells. The TYK2i and the JAK2i efficiently blocked IL-12 and IFN-γ-induced activation of PBMCs from STAT4 risk patients, respectively.ConclusionsT cells from patients with SLE carrying the STAT4 risk allele rs7574865[T] display an augmented response to IL-12 and IFN-α. This subset of patients may benefit from JAKi treatment.

scholarly journals Immune-Based Prediction of COVID-19 Severity and Chronicity Decoded Using Machine Learning

2021 ◽  
Vol 12 ◽  
Author(s):  
Bruce K. Patterson ◽  
Jose Guevara-Coto ◽  
Ram Yogendra ◽  
Edgar B. Francisco ◽  
Emily Long ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell Activation ◽  
Cell Activation ◽  
Mononuclear Cells ◽  
Severe Disease ◽  
Healthy Controls ◽  
Binary Classifier ◽  
Activated T Cells ◽  
Peripheral Blood Mononuclear ◽  
Ifn Γ

Expression of CCR5 and its cognate ligands have been implicated in COVID-19 pathogenesis, consequently therapeutics directed against CCR5 are being investigated. Here, we explored the role of CCR5 and its ligands across the immunologic spectrum of COVID-19. We used a bioinformatics approach to predict and model the immunologic phases of COVID so that effective treatment strategies can be devised and monitored. We investigated 224 individuals including healthy controls and patients spanning the COVID-19 disease continuum. We assessed the plasma and isolated peripheral blood mononuclear cells (PBMCs) from 29 healthy controls, 26 Mild-Moderate COVID-19 individuals, 48 Severe COVID-19 individuals, and 121 individuals with post-acute sequelae of COVID-19 (PASC) symptoms. Immune subset profiling and a 14-plex cytokine panel were run on all patients from each group. B-cells were significantly elevated compared to healthy control individuals (P<0.001) as was the CD14+, CD16+, CCR5+ monocytic subset (P<0.001). CD4 and CD8 positive T-cells expressing PD-1 as well as T-regulatory cells were significantly lower than healthy controls (P<0.001 and P=0.01 respectively). CCL5/RANTES, IL-2, IL-4, CCL3, IL-6, IL-10, IFN-γ, and VEGF were all significantly elevated compared to healthy controls (all P<0.001). Conversely GM-CSF and CCL4 were in significantly lower levels than healthy controls (P=0.01). Data were further analyzed and the classes were balanced using SMOTE. With a balanced working dataset, we constructed 3 random forest classifiers: a multi-class predictor, a Severe disease group binary classifier and a PASC binary classifier. Models were also analyzed for feature importance to identify relevant cytokines to generate a disease score. Multi-class models generated a score specific for the PASC patients and defined as S1 = (IFN-γ + IL-2)/CCL4-MIP-1β. Second, a score for the Severe COVID-19 patients was defined as S2 = (IL-6+sCD40L/1000 + VEGF/10 + 10*IL-10)/(IL-2 + IL-8). Severe COVID-19 patients are characterized by excessive inflammation and dysregulated T cell activation, recruitment, and counteracting activities. While PASC patients are characterized by a profile able to induce the activation of effector T cells with pro-inflammatory properties and the capacity of generating an effective immune response to eliminate the virus but without the proper recruitment signals to attract activated T cells.

scholarly journals Identification and Characterization of Neospora caninum Cyclophilin That Elicits Gamma Interferon Production

2005 ◽  
Vol 73 (8) ◽  
pp. 5093-5100 ◽  
Author(s):  
Wenbin Tuo ◽  
Raymond Fetterer ◽  
Mark Jenkins ◽  
J. P. Dubey
Keyword(s):  
T Cells ◽  
Mononuclear Cells ◽  
Culture Supernatant ◽  
Neospora Caninum ◽  
Secretory Protein ◽  
Gamma Interferon ◽  
Dependent Manner ◽  
Peripheral Blood Mononuclear ◽  
Calculated Molecular Mass ◽  
Ifn Γ

ABSTRACT Gamma interferon (IFN-γ) response is essential to the development of a host protective immunity in response to infections by intracellular parasites. Neosporosis, an infection caused by the intracellular protozoan parasite Neospora caninum, is fatal when there is a complete lack of IFN-γ in the infected host. However, the mechanism by which IFN-γ is elicited by the invading parasite is unclear. This study has identified a microbial protein in the N. caninum tachyzoite N. caninum cyclophilin (NcCyP) as a major component of the parasite responsible for the induction of IFN-γ production by bovine peripheral blood mononuclear cells (PBMC) and antigen-specific CD4+ T cells. NcCyP has high sequence homology (86%) with Toxoplasma gondii 18-kDa CyP with a calculated molecular mass of 19.4 kDa. NcCyP is a secretory protein with a predicted signal peptide of 17 amino acids. Abundant NcCyP was detected in whole-cell N. caninum tachyzoite lysate antigen (NcAg) and N. caninum tachyzoite culture supernatant. In N. caninum tachyzoite culture supernatant, three NcCyP bands of 19, 22, and 24 kDa were identified. NcAg stimulated high levels of IFN-γ production by PBMC and CD4+ T cells. The IFN-γ-inducing effect of NcAg was blocked by cyclosporine, a specific ligand for CyP, in a dose-dependent manner. Furthermore, cyclosporine abolished IFN-γ production by PBMC from naïve cows as well as PBMC and CD4+ T cells from infected/immunized cows. These results indicate that the N. caninum tachyzoite naturally produces a potent IFN-γ-inducing protein, NcCyP, which may be important for parasite survival as well as host protection.

scholarly journals Single-cell multi-omics analysis of the immune response in COVID-19

2021 ◽  
Author(s):  
Emily Stephenson ◽  
◽  
Gary Reynolds ◽  
Rachel A. Botting ◽  
Fernando J. Calero-Nieto ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cells ◽  
Single Cell ◽  
Mononuclear Cells ◽  
Severe Disease ◽  
Effector Memory ◽  
Peripheral Blood Mononuclear ◽  
Cross Sectional ◽  
Hematopoietic Stem ◽  
Symptomatic Disease

AbstractAnalysis of human blood immune cells provides insights into the coordinated response to viral infections such as severe acute respiratory syndrome coronavirus 2, which causes coronavirus disease 2019 (COVID-19). We performed single-cell transcriptome, surface proteome and T and B lymphocyte antigen receptor analyses of over 780,000 peripheral blood mononuclear cells from a cross-sectional cohort of 130 patients with varying severities of COVID-19. We identified expansion of nonclassical monocytes expressing complement transcripts (CD16+C1QA/B/C+) that sequester platelets and were predicted to replenish the alveolar macrophage pool in COVID-19. Early, uncommitted CD34+ hematopoietic stem/progenitor cells were primed toward megakaryopoiesis, accompanied by expanded megakaryocyte-committed progenitors and increased platelet activation. Clonally expanded CD8+ T cells and an increased ratio of CD8+ effector T cells to effector memory T cells characterized severe disease, while circulating follicular helper T cells accompanied mild disease. We observed a relative loss of IgA2 in symptomatic disease despite an overall expansion of plasmablasts and plasma cells. Our study highlights the coordinated immune response that contributes to COVID-19 pathogenesis and reveals discrete cellular components that can be targeted for therapy.

scholarly journals Gene expression profile of human T cells following a single stimulation of peripheral blood mononuclear cells with anti-CD3 antibodies

BMC Genomics ◽  
2019 ◽  
Vol 20 (1) ◽  
Author(s):  
Isabel Garcia Sousa ◽  
Kelly Cristina Rodrigues Simi ◽  
Manuela Maragno do Almo ◽  
Maryani Andressa Gomes Bezerra ◽  
Gero Doose ◽  
...  
Keyword(s):  
Gene Expression ◽  
T Cells ◽  
Gene Expression Profile ◽  
Peripheral Blood Mononuclear Cells ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Peripheral Blood Mononuclear ◽  
Human T Cells ◽  
Blood Mononuclear Cells ◽  
Stimulation Of

scholarly journals Lactobacilli and Streptococci Induce Interleukin-12 (IL-12), IL-18, and Gamma Interferon Production in Human Peripheral Blood Mononuclear Cells

1998 ◽  
Vol 66 (12) ◽  
pp. 6058-6062 ◽  
Author(s):  
Minja Miettinen ◽  
Sampsa Matikainen ◽  
Jaana Vuopio-Varkila ◽  
Jaana Pirhonen ◽  
Kari Varkila ◽  
...  
Keyword(s):  
Peripheral Blood Mononuclear Cells ◽  
Peripheral Blood ◽  
Protein Production ◽  
Mononuclear Cells ◽  
Human Peripheral Blood ◽  
Gamma Interferon ◽  
Cytokine Gene Expression ◽  
Peripheral Blood Mononuclear ◽  
Blood Mononuclear Cells ◽  
Ifn Γ

ABSTRACT Human peripheral blood mononuclear cells (PBMC) were stimulated with three nonpathogenic Lactobacillus strains and with one pathogenic Streptococcus pyogenes strain, and cytokine gene expression and protein production were analyzed. All bacteria strongly induced interleukin-1β (IL-1β), IL-6, and tumor necrosis factor alpha mRNA expression and protein production. S. pyogenes was the most potent inducer of secretion of IL-12 and gamma interferon (IFN-γ), and two of three Lactobacillusstrains induced IL-12 and IFN-γ production. All strains induced IL-18 protein production. IL-10 and IL-4 production was induced weakly and not at all, respectively. Our data show that nonpathogenic lactobacilli and pathogenic streptococci can induce Th1 type cytokines IL-12, IL-18, and IFN-γ in human PBMC.

scholarly journals Response to Superantigen Stimulation in Peripheral Blood Mononuclear Cells from Children Perinatally Infected with Human Immunodeficiency Virus and Receiving Highly Active Antiretroviral Therapy

2004 ◽  
Vol 11 (5) ◽  
pp. 957-962 ◽  
Author(s):  
Thomas W. McCloskey ◽  
Viraga Haridas ◽  
Lucy Pontrelli ◽  
Savita Pahwa
Keyword(s):  
Human Immunodeficiency Virus ◽  
T Cells ◽  
Antiretroviral Therapy ◽  
Highly Active Antiretroviral Therapy ◽  
Mononuclear Cells ◽  
Peripheral Blood Mononuclear ◽  
Highly Active ◽  
Immunodeficiency Virus ◽  
Blood Mononuclear Cells ◽  
Ifn Γ

ABSTRACT Our understanding of the pathogenesis of perinatal human immunodeficiency virus (HIV) infection is still evolving. We sought to characterize the response to the bacterial superantigen Staphylococcus enterotoxin B (SEB) of lymphocytes from HIV-infected children receiving treatment with highly active antiretroviral therapy (HAART). Using the flow cytometric methodology, we quantified apoptosis, proliferation, cytokine production, and activation antigen upregulation in CD4 and CD8 T lymphocytes following in vitro stimulation of peripheral blood mononuclear cells (PBMCs) with SEB. The levels of proliferation, CD4 interleukin-2 (IL-2) production, CD8 gamma interferon (IFN-γ) production, and upregulation of CD69 expression by cells from HIV-infected children were indistinguishable from those by cells from controls. However, stimulation with SEB dramatically decreased the ratio of resting apoptotic cells to cycling apoptotic cells in the controls but not in the patients. In addition, unstimulated spontaneous apoptosis of CD4 T cells remained greater in the patients than in the controls. The percentages of IL-2-positive CD8 T cells and IFN-γ-positive CD4 T cells following SEB stimulation were significantly lower in the patients than in the controls. Our multiparameter approach was able to demonstrate differences in lymphocyte superantigen responsiveness in HIV-infected children receiving HAART in comparison to that in uninfected controls, notably, an apoptotic versus a proliferative response to stimulation.

Sign in / Sign up

Export Citation Format

Share Document