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 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 Anti-lymphocyte globulin stimulates normal human T cells to proliferate and to release lymphokines in vitro. A study at the clonal level

Blood ◽  
1988 ◽  
Vol 72 (3) ◽  
pp. 956-963
Author(s):  
GC Barbano ◽  
A Schenone ◽  
S Roncella ◽  
R Ghio ◽  
A Corcione ◽  
...  
Keyword(s):  
T Cells ◽  
Mononuclear Cells ◽  
Human Peripheral Blood ◽  
Interleukin 2 ◽  
Suppressor Cells ◽  
Peripheral Blood Mononuclear ◽  
Gm Csf ◽  
Recombinant Interleukin 2 ◽  
Macrophage Colony

Abstract Human peripheral blood mononuclear cells (PBMC) were stimulated in vitro with anti-lymphocyte globulin (ALG), and the phenotypic and functional properties of the blasts obtained were investigated. When stained with monoclonal antibodies (MoAbs), all of the blasts were identified as T cells that expressed predominantly the CD4 phenotype (70% of the cells). The remaining blasts were CD8+. These findings demonstrate that ALG stimulates both helper-inducer and cytotoxic- suppressor cells at random since the CD4 to CD8 ratio in the stimulated blasts was the same as in resting PBMC. This ratio is different from that observed in short-term cultures of T cells stimulated with phytohemagglutinin (PHA) under the same conditions (CD4 to CD8 ratio less than 1). ALG-stimulated T cells were cloned by limiting dilution in the presence of recombinant Interleukin-2 (rIL-2). The clones obtained were expanded and maintained in long term cultures with rIL-2. Thirty-two clones were tested for their capacity of producing colony stimulating activity (CSA) or burst promoting activity (BPA). Twenty- eight of them produced CSA and 12 produced BPA. No correlation was found between the surface phenotype and the ability of the clones to produce CSA or BPA (ie, both the CD4+ and CD8+ clones released the cytokines). When 16 of the same clones were tested for II-2 and gamma interferon (gamma IFN) production, 12 were found to be gamma INF and IL- 2 producers. All of the gamma IFN producers also released IL-2, whereas in the single clones no correlation was found with the capacity of releasing BPA and CSA. Supernatants from selected T-cell clones were also tested for hematopoietic growth factor activities in the presence of neutralizing antisera to human granulocyte-macrophage colony stimulating factor (GM-CSF) or to Interleukin-3 (IL-3). It was found that most CSA was attributable to GM-CSF, whereas BPA was mainly related to the presence of IL-3.

scholarly journals Cytokine and Chemokine Profiles following Vaccination with Human Papillomavirus Type 16 L1 Virus-Like Particles

2007 ◽  
Vol 14 (8) ◽  
pp. 984-989 ◽  
Author(s):  
Alfonso García-Piñeres ◽  
Allan Hildesheim ◽  
Lori Dodd ◽  
Troy J. Kemp ◽  
Marcus Williams ◽  
...  
Keyword(s):  
Human Papillomavirus ◽  
Mononuclear Cells ◽  
Interleukin 2 ◽  
Neutralizing Antibody ◽  
Antibody Responses ◽  
Peripheral Blood Mononuclear ◽  
Virus Like Particles ◽  
Cytokine Bead Array ◽  
Macrophage Colony

ABSTRACT To determine the systemic cytokine pattern induced by vaccination with human papillomavirus (HPV) L1 virus-like particles (VLP), we analyzed 22 different cytokines in culture supernatants of L1 VLP-stimulated peripheral blood mononuclear cells from vaccine (n = 19) and placebo (n = 7) recipients at months 0 and 2 after vaccination, using a multiplex cytokine bead array. In vaccine recipients, incubation with L1 VLP in vitro led to a statistically significant increase in production of Th1 (granulocyte-macrophage colony-stimulating factor, interleukin-2 [IL-2], gamma interferon; P < 0.0007) and Th2 (IL-4, IL-5, IL-10, IL-13; P < 0.0017) cytokines and the chemokine IP-10 (P = 0.0021) at month 2 after immunization, compared to levels seen prior to vaccination. These responses were not seen in placebo recipients. Cytokine and neutralizing antibody responses to vaccination followed the same pattern, with the highest antibody responses seen for subjects with higher cytokine responses. Cytokine profiling studies using samples from efficacy trials may provide important information about discriminators of long-term protection against HPV.

scholarly journals Induction of Cell-Mediated Immunity to Staphylococcus aureus in the Mouse Mammary Gland by Local Immunization with a Live Attenuated Mutant

2002 ◽  
Vol 70 (8) ◽  
pp. 4254-4260 ◽  
Author(s):  
Marisa I. Gómez ◽  
Daniel O. Sordelli ◽  
Fernanda R. Buzzola ◽  
Verónica E. García
Keyword(s):  
Staphylococcus Aureus ◽  
T Cells ◽  
Mammary Gland ◽  
Mononuclear Cells ◽  
Regional Lymph Node ◽  
Interleukin 2 ◽  
Mouse Mammary Gland ◽  
Cell Mediated Immunity ◽  
Ifn Γ

ABSTRACT The efficacy of intramammary (Ima) immunization with a live attenuated (la) Staphylococcus aureus mutant to protect the mouse mammary gland from infection has previously been established. The present study was aimed at evaluating whether Ima immunization with la-S. aureus can induce cell-mediated immune responses to the pathogen within the mammary gland. Mice were immunized by Ima route with la-S. aureus, and regional lymph node mononuclear cells were obtained thereafter. A higher expression of the interleukin-2 receptor was found on B and T cells from immunized mice when they were compared with control mice. Immunization with la-S. aureus induced strong proliferative responses to S. aureus. Moreover, significantly increased levels of gamma interferon (IFN-γ) were produced by CD4+ T cells when lymphocytes from immunized mice, but not from control mice, were cultured in the presence of staphylococcal antigens. Moreover, a significant increase in the percentage of IFN-γ-producing CD4+ and CD8+ T cells was observed after S. aureus Ima challenge in immunized mice compared to challenged control mice. Our results demonstrated that Ima immunization with la-S. aureus induced primed lymphocyte populations capable of responding against staphylococcal antigens during in vitro stimulation, as well as during in vivo infection by S. aureus. CD4+ and CD8+ T cells appear to be the main lymphocyte subpopulations involved in this response. It is suggested that IFN-γ production induced by Ima immunization may play a pivotal role in the eradication of intracellular staphylococci.

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 Polyfunctional T Lymphocytes Are in the Peripheral Blood of Donors Naturally Immune to Coccidioidomycosis and Are Not Induced by Dendritic Cells

2009 ◽  
Vol 78 (1) ◽  
pp. 309-315 ◽  
Author(s):  
Lance Nesbit ◽  
Suzanne M. Johnson ◽  
Demosthenes Pappagianis ◽  
Neil M. Ampel
Keyword(s):  
Dendritic Cells ◽  
T Lymphocytes ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Interleukin 2 ◽  
High Expression ◽  
Peripheral Blood Mononuclear ◽  
Necrosis Factor Alpha ◽  
Ifn Γ

ABSTRACT Coccidioidomycosis is a fungal infection endemic in the southwestern United States that is increasing in incidence. While cellular immunity correlates with protection from clinical illness, the precise elements of that response are undefined. Using the coccidioidal antigen preparation T27K and multiparametric flow cytometry, the in vitro frequency of polyfunctional T lymphocytes in the peripheral blood of naturally immune healthy donors and those who were nonimmune was determined. Polyfunctional CD4 lymphocytes, defined as producing intracellular interleukin 2 (IL-2), gamma interferon (IFN-γ), and tumor necrosis factor alpha simultaneously, had a frequency of 137 per 400,000 events among peripheral blood mononuclear cells (PBMC) of immune donors compared to 11 per 400,000 PBMC from nonimmune donors (P = 0.03). When monocyte-derived mature dendritic cells pulsed with T27K (mDCT27K) were used for antigen presentation, the frequency of polyfunctional CD4 T lymphocytes did not significantly increase for either group, although mDCT27K did significantly increase the concentrations of IL-2 and IFN-γ released by PBMC from nonimmune donors (P = 0.02). After in vitro stimulation with T27K, polyfunctional CD4 and CD8 lymphocytes of PBMC from immune donors had a mixture of low- and high-expression CCR7 cells, suggesting both effector and central memory, compared with predominantly high-expression CCR7 cells when PBMC were incubated with the mitogen phytohemagglutinin (P = 0.03). These data demonstrate the presence of polyfunctional T lymphocytes in the peripheral blood of individuals with coccidioidal immunity and suggest a model for the in vitro testing of vaccine candidates for coccidioidomycosis.

scholarly journals Differences in Gamma Interferon Production In Vitro Predict the Pace of the In Vivo Response to Leishmania amazonensis in Healthy Volunteers

2001 ◽  
Vol 69 (12) ◽  
pp. 7453-7460 ◽  
Author(s):  
M. M. L. Pompeu ◽  
C. Brodskyn ◽  
M. J. Teixeira ◽  
J. Clarêncio ◽  
J. Van Weyenberg ◽  
...  
Keyword(s):  
Mononuclear Cells ◽  
Interleukin 10 ◽  
Gamma Interferon ◽  
Leishmania Amazonensis ◽  
Cell Mediated Immunity ◽  
Peripheral Blood Mononuclear ◽  
Necrosis Factor Alpha ◽  
Ifn Γ

ABSTRACT The initial encounter of Leishmania cells and cells from the immune system is fundamentally important in the outcome of infection and determines disease development or resistance. We evaluated the anti-Leishmania amazonensis response of naive volunteers by using an in vitro priming (IVP) system and comparing the responses following in vivo vaccination against the same parasite. In vitro stimulation allowed us to distinguish two groups of individuals, those who produced small amounts of gamma interferon (IFN-γ) (n = 16) (low producers) and those who produced large amounts of this cytokine (n = 16) (high producers). IFN-γ production was proportional to tumor necrosis factor alpha and interleukin 10 (IL-10) levels but did not correlate with IL-5 production. Volunteers who produced small amounts of IFN-γ in vitro remained low producers 40 days after vaccination, whereas high producers exhibited increased IFN-γ production. However, 6 months after vaccination, all individuals tested produced similarly high levels of IFN-γ upon stimulation of their peripheral blood mononuclear cells with Leishmania promastigotes, indicating that low in vitro producers respond slowly in vivo to vaccination. In high IFN-γ producers there was an increased frequency of activated CD8+ T cells both in vitro and in vivo compared to the frequency in low producers, and such cells were positive for IFN-γ as determined by intracellular staining. Such findings suggest that IVP responses can be used to predict the pace of postvaccination responses of test volunteers. Although all vaccinated individuals eventually have a potent anti-Leishmania cell-mediated immunity (CMI) response, a delay in mounting the CMI response may influence resistance against leishmaniasis.

scholarly journals Anti-lymphocyte globulin stimulates normal human T cells to proliferate and to release lymphokines in vitro. A study at the clonal level

Blood ◽  
1988 ◽  
Vol 72 (3) ◽  
pp. 956-963 ◽  
Author(s):  
GC Barbano ◽  
A Schenone ◽  
S Roncella ◽  
R Ghio ◽  
A Corcione ◽  
...  
Keyword(s):  
T Cells ◽  
Mononuclear Cells ◽  
Human Peripheral Blood ◽  
Interleukin 2 ◽  
Suppressor Cells ◽  
Peripheral Blood Mononuclear ◽  
Gm Csf ◽  
Recombinant Interleukin 2 ◽  
Macrophage Colony

Human peripheral blood mononuclear cells (PBMC) were stimulated in vitro with anti-lymphocyte globulin (ALG), and the phenotypic and functional properties of the blasts obtained were investigated. When stained with monoclonal antibodies (MoAbs), all of the blasts were identified as T cells that expressed predominantly the CD4 phenotype (70% of the cells). The remaining blasts were CD8+. These findings demonstrate that ALG stimulates both helper-inducer and cytotoxic- suppressor cells at random since the CD4 to CD8 ratio in the stimulated blasts was the same as in resting PBMC. This ratio is different from that observed in short-term cultures of T cells stimulated with phytohemagglutinin (PHA) under the same conditions (CD4 to CD8 ratio less than 1). ALG-stimulated T cells were cloned by limiting dilution in the presence of recombinant Interleukin-2 (rIL-2). The clones obtained were expanded and maintained in long term cultures with rIL-2. Thirty-two clones were tested for their capacity of producing colony stimulating activity (CSA) or burst promoting activity (BPA). Twenty- eight of them produced CSA and 12 produced BPA. No correlation was found between the surface phenotype and the ability of the clones to produce CSA or BPA (ie, both the CD4+ and CD8+ clones released the cytokines). When 16 of the same clones were tested for II-2 and gamma interferon (gamma IFN) production, 12 were found to be gamma INF and IL- 2 producers. All of the gamma IFN producers also released IL-2, whereas in the single clones no correlation was found with the capacity of releasing BPA and CSA. Supernatants from selected T-cell clones were also tested for hematopoietic growth factor activities in the presence of neutralizing antisera to human granulocyte-macrophage colony stimulating factor (GM-CSF) or to Interleukin-3 (IL-3). It was found that most CSA was attributable to GM-CSF, whereas BPA was mainly related to the presence of IL-3.

scholarly journals Gamma Interferon Production by Bovine γδ T Cells following Stimulation with Mycobacterial Mycolylarabinogalactan Peptidoglycan

2004 ◽  
Vol 72 (8) ◽  
pp. 4612-4618 ◽  
Author(s):  
B. Vesosky ◽  
O. C. Turner ◽  
J. Turner ◽  
I. M. Orme
Keyword(s):  
T Cells ◽  
Cell Wall ◽  
Sodium Dodecyl ◽  
Interleukin 2 ◽  
Γδ T Cells ◽  
Cell Receptor ◽  
Gamma Interferon ◽  
Ifn Γ ◽  
Mycobacterial Cell Wall

ABSTRACT A large percentage of lymphocytes in the blood of cattle express the γδ T-cell receptor, but specific functions for these cells have not yet been clearly defined. There is evidence, however, that human, murine, and bovine γδ T cells have a role in the immune response to mycobacteria. This study investigated the ability of bovine γδ T cells to expand and produce gamma interferon (IFN-γ) in response to stimulation with mycobacterial products. Bovine γδ T cells, isolated from the peripheral blood of healthy cattle, expanded following in vitro stimulation with live mycobacteria, mycobacterial crude cell wall extract, and Mycobacterium bovis culture filtrate proteins. In addition, purified γδ T cells, cocultured with purified monocytes and interleukin-2, consistently produced significant amounts of IFN-γ in response to mycobacterial cell wall. The IFN-γ-inducing component of the cell wall was further identified as a proteolytically resistant, non-sodium dodecyl sulfate-soluble component of the mycolylarabinogalactan peptidoglycan.

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.

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