scholarly journals Mechanisms of T-Lymphocyte Accumulation during Experimental Pleural Infection Induced by Mycobacterium bovis BCG

2008 ◽  
Vol 76 (12) ◽  
pp. 5686-5693 ◽  
Author(s):  
Mariana C. Souza ◽  
Carmen Penido ◽  
Maria F. S. Costa ◽  
Maria Graças Henriques
Keyword(s):  
T Lymphocytes ◽  
Mycobacterium Bovis ◽  
T Lymphocyte ◽  
Mononuclear Cells ◽  
Interleukin 2 ◽  
Pleural Space ◽  
T Lymphocyte Proliferation ◽  
Pleural Infection ◽  
Ifn Γ

ABSTRACT Tuberculous pleurisy is a frequent extrapulmonary manifestation characterized by accumulation of fluid and inflammatory cells in the pleural space. Here, we investigated the mechanisms of T-lymphocyte accumulation in the pleural space by using a murine model of pleurisy induced by Mycobacterium bovis BCG. Intrathoracic (i.t.) injection of BCG (4.5 × 105 bacteria/cavity) induced accumulation of T lymphocytes in the pleural cavities of C57BL/6 mice. We observed the presence of CFU in pleural washes conducted 1, 2, 3, 7, and 15 days after pleurisy induction. Pretreatment with fucoidan inhibited T-lymphocyte accumulation at 1 day, but not at 15 days, after BCG-induced pleurisy. Accordingly, adoptive transfer of fluorescein isothiocyanate-labeled blood mononuclear cells to infected mice showed that T lymphocytes migrated into the pleural cavity 1 day (but not 15 days) after BCG injection. Cell-free pleural wash fluids recovered from mice 1 day after BCG i.t. stimulation (day 1 BCG-PW), but not day 7 or day 15 BCG-PW, induced in vitro T-cell transmigration, which was dependent on L-, P-, and E-selectins. In contrast, day 7 BCG-PW (but not day 1 BCG-PW) induced in vitro T-lymphocyte proliferation via interleukin-2 (IL-2) and gamma interferon (IFN-γ). Accordingly, in vivo IL-2 or IFN-γ neutralization abolished T-lymphocyte accumulation 7 days after pleurisy induction. Our results demonstrate that pleural infection induced by BCG leads to T-lymphocyte accumulation in two waves. The acute phase depends on selectin-mediated migration, while the second wave of T-lymphocyte accumulation seems to depend on a local proliferation induced by cytokines produced in situ.

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 Differential Effects of Tea Extracts on Growth and Cytokine Production by Normal and Leukemic Human Leukocytes

2012 ◽  
Vol 2 (4) ◽  
pp. 72 ◽  
Author(s):  
Diana Bayer ◽  
Jonathon Jansen ◽  
Lisa A. Beltz
Keyword(s):  
T Lymphocytes ◽  
T Lymphocyte ◽  
Mononuclear Cells ◽  
Cytokine Production ◽  
Lymphoblastic Leukemia ◽  
Interleukin 2 ◽  
Leukemic Cells ◽  
Leukemia Cells ◽  
Peripheral Blood Mononuclear ◽  
Normal Cells

Background: Tea is one of the world’s most highly consumed beverages, second only to water. It is affordable and abundant and thus has great potential for improving health of those in both developed and developing areas. Green, oolong, and black teas differ in the extent of fermentation and types of bioactive polyphenols produced. Green tea and its major polyphenol decrease growth of some cancer cells and effect production of immune system cytokines. This study compares the effects of different types of tea extracts on viability and cytokine production by normal and leukemic human T lymphocytes. Generation of the toxic reactive oxygen species H2O2 by extracts was also examined.Methods: The Jurkat T lymphoblastic leukemia cells and mitogen-stimulated normal human peripheral blood mononuclear cells were used in this study. Cell viability was determined by (3-4,5-dimethylthiamizol-2-yl)-diphenyltetrazolium bromide) assay and production of interleukin-2 by Enzyme-Linked ImmunoSorbent Assay. Levels of H2O2 generated by tea extracts were determined using the xylenol-orange method.Results: We found that green, oolong, and black tea extracts differentially effect the growth and viability of T lymphoblastic leukemia cells and normal peripheral blood mononuclear cells, substantially decreasing both growth and viability of leukemic T lymphocytes and having much lesser effects on their normal counterparts. Tea extracts also had differential effects on the production of the T lymphocyte growth factor interleukin-2, significantly decreasing production by leukemic cells while having only minor effects on normal cells. All three extracts induced H2O2 generation, with green and oolong tea extracts having the greatest effect. Leukemic cells were much more susceptible to growth inhibition and killing by H2O2 than normal lymphocytes. Conclusions: The three tea extracts studied altered leukemic T lymphocyte functions, decreasing cell viability, growth, and production of a major cell growth factor and the H2O2 generated by solutions of extracts may be partially responsible. Normal cells were affected to a far lesser degree by tea extracts and are also more resistant to killing by H2O2 than leukemic cells. This study has implications for using tea extracts for chemotherapeutic and immunomodulatory purposes.Key Words: Tea extracts, interleukin-2, hydrogen peroxide, leukemia, T lymphocytes

scholarly journals Bovine Immune Response to Inoculation with Neospora caninum Surface Antigen SRS2 Lipopeptides Mimics Immune Response to Infection with Live Parasites

2008 ◽  
Vol 15 (4) ◽  
pp. 659-667 ◽  
Author(s):  
Timothy V. Baszler ◽  
Varda Shkap ◽  
Waithaka Mwangi ◽  
Christopher J. Davies ◽  
Bruce A. Mathison ◽  
...  
Keyword(s):  
Immune Response ◽  
Immune Responses ◽  
Dna Vaccine ◽  
T Lymphocyte ◽  
Mononuclear Cells ◽  
Neospora Caninum ◽  
Lymphocyte Activation ◽  
T Lymphocyte Activation ◽  
T Lymphocyte Proliferation ◽  
Ifn Γ

ABSTRACT Infection of cattle with Neospora caninum protozoa, the causative agent of bovine protozoal abortion, results in robust cellular and humoral immune responses, particularly CD4+ T-lymphocyte activation and gamma interferon (IFN-γ) secretion. In the present study, N. caninum SRS2 (NcSRS2) T-lymphocyte-epitope-bearing subunits were incorporated into DNA and peptide preparations to assess CD4+ cell proliferation and IFN-γ T-lymphocyte-secretion immune responses in cattle with predetermined major histocompatibility complex (MHC) genotypes. In order to optimize dendritic-cell processing, NcSRS2 DNA vaccine was delivered with granulocyte macrophage-colony-stimulating factor and Flt3 ligand adjuvant. The synthesized NcSRS2 peptides were coupled with a palmitic acid molecule (lipopeptide) and delivered with Freund's adjuvant. Cattle vaccinated with NcSRS2 DNA vaccine alone did not induce T-lymphocyte activation or IFN-γ secretion, whereas subsequent booster inoculation with NcSRS2-lipopeptides induced robust NcSRS2-specific immune responses. Compared to the response in control animals, NcSRS2-lipopeptide-immunized cattle had significantly increased NcSRS2-specific T-lymphocyte proliferation, numbers of IFN-γ-secreting peripheral blood mononuclear cells, and immunoglobulin G1 (IgG1) and IgG2a antibody levels. The findings show that N. caninum NcSRS2 subunits bearing T-lymphocyte epitopes induced cell-mediated immune responses similar to the protective immune responses previously described against live parasite infection, namely T-lymphocyte activation and IFN-γ secretion. The findings support the investigation of NcSRS2 immunogens for protection against N. caninum-induced fetal infection and abortion in cattle.

scholarly journals PROTEIN REKOMBINAN 38 KDA MYCOBAKTERIUM TUBERKULOSIS DAPAT MENGIMBAS PEMBUATAN INTERLEUKIN-2 DAN INTERFERON-γ LIMFOSIT T DI KULTUR SEL MONONUKLEAR DARAH TEPI

2018 ◽  
Vol 22 (2) ◽  
pp. 151
Author(s):  
Maimun Z Arthamin ◽  
Singgih Pujo Wahono ◽  
Antiek Primardianti ◽  
Ati Rastini ◽  
Tri Wahju Astuti ◽  
...  
Keyword(s):  
Immune Response ◽  
T Lymphocytes ◽  
Recombinant Protein ◽  
Vaccine Development ◽  
Interleukin 2 ◽  
Development Program ◽  
In Vitro Study ◽  
Cell Mediated Immunity ◽  
Ifn Γ

Tuberculosis (TB) is caused by Mycobacterium tuberculosis (M.tb) and is one of the significant mortality causes WHO (2012). Theprimary immune response in TB pathogenesis is Cell Mediated Immunity (CMI), roled by T lymphocytes. Interleukin-2 (IL-2) is a growthfactor for T lymphocytes. Gamma Interferon is the key cytokine in M.tb infection control, synthezised by T lymphocytes. An effectivevaccination strategy is achieved by giving vaccine which is able to stimulate T lymphocytes in synthezising cytokines. The 38 kDa M.tbprotein is potential in the vaccine development program, because it has specific epitopes for T lymphocytes. The aim of this study was toknow how to determine that the 38 kDa recombinant protein of M.tb Malang strain could induce cellular immune response by IL-2 andIFN-γ synthezised by T lymphocytes. The study was carried out by an experimental in vitro study on PBMC from healthy endemic subjects,those having TB contact, and the TB patients themselves. PBMC from subjects was cultured with 38 kDa recombinant protein of M.tbMalang strain, with PPD and without any protein. The analysis of IL-2 and IFN-γ used flowcytometry. The result showed that the highestpercentage of IL-2 was found in the culture with 38 kDa recombinant protein of M.tb Malang strain, in healthy endemic (p=0.000)and in those who had TB contact (p=0.000). the highest percentage of IFN-γ was found in the culture with 38 kDa recombinant proteinof M.tb Malang strain, in healthy endemic (p=0.007) and those who had TB contact (p = 0.105). The 38 kDa recombinant proteinof M.tb Malang strain was able to induce IL-2 and IFN-γ synthezised by TCD3+ lymphocytes from healthy endemic subjects and thosewho had TB contact.

scholarly journals Defective interleukin 2 production in patients after bone marrow transplantation and in vitro restoration of defective T lymphocyte proliferation by highly purified interleukin 2

Blood ◽  
1984 ◽  
Vol 64 (2) ◽  
pp. 380-385 ◽  
Author(s):  
K Welte ◽  
N Ciobanu ◽  
MA Moore ◽  
S Gulati ◽  
RJ O'Reilly ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Mononuclear Cells ◽  
Interleukin 2 ◽  
Autologous Bone Marrow ◽  
Hematologic Malignancies ◽  
Allogeneic Bone ◽  
Peripheral Blood Mononuclear ◽  
T Lymphocyte Proliferation ◽  
Conditioning Regimens

Using OKT3 monoclonal antibody as a mitogen, we have studied interleukin 2 (IL2) production and proliferation in peripheral blood mononuclear cells (PBMC) of 23 patients receiving bone marrow transplants. Twenty patients were recipients of allogeneic bone marrow for treatment of hematologic malignancies, aplastic anemias (AA), or severe combined immunodeficiencies (SCID). Three patients with Hodgkin's disease or neuroblastoma received autologous bone marrow. Endogenous IL2 production was not detectable (less than 0.2 U/mL) in PBMC of 18 patients and was very low in PBMC from five patients (0.5 to 1.5 U/mL), as compared to normal controls (median 3.5 U/mL) or pretransplant patients (median 1.5 U/mL). The low IL2 production was associated with defective OKT3-induced proliferation of PBMC in 19 of 23 patients studied. In the first 6 months after BMT, 14 of 15 patients (93%) showed defective proliferation of PBMC as compared to five of eight patients (63%) tested between 7 and 18 months after BMT (P less than .1). In all but three patients, addition of highly purified human lymphocyte IL2 (hpIL2) restored OKT3-induced proliferation of PBMC to within the normal range. This study demonstrates that PBMC in patients after BMT have a defect of IL2 production but are able to express IL2 receptors in response to OKT3 antibody and to proliferate normally upon addition of hpIL2. PBMC of all patients showed similar functional defects, whether or not they received additional therapy, including various conditioning regimens prior to BMT and immunosuppressive therapy after BMT. These observations suggest that T cell defects after BMT are most likely secondary to quantitative or qualitative defects of transplanted T lymphocytes or their precursors.

Depleting Autologous Activated CD4+ t Lymphocytes Increased Generation of Colony-Forming-Cells(CFC) in Patients with Myelodysplastic Syndromes

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 5092-5092
Author(s):  
Zheng Zhang ◽  
Xiao Li ◽  
Qianqiao Zhang ◽  
Ying Tao ◽  
Qi He
Keyword(s):  
T Cells ◽  
T Lymphocytes ◽  
T Lymphocyte ◽  
Mononuclear Cells ◽  
Fish Analysis ◽  
Low Grade ◽  
Healthy Donors ◽  
Magnetic Sorting ◽  
Colony Forming Cell

Abstract Objective To investigate how autoimmune mechanism playing a role in generation of colony-forming-cells(CFC), bone mononuclear cells(BMNC) from MDS were removed of autologous activated CD4+ T cells in vitro and cultured to find out effect of T cells on MDS hemopietic progenitor. Methods BMNC from 25 patients with low-grade MDS and 5 normal donors were depleted of CD4+CCR5+ T lymphocytes using magnetic sorting. Depleted and plused CD4+CCR5+ T BMNC were seeded onto methycellulose and the correlation of colony-forming-cell (CFC) number and the polarization of T cells were analyzed, the generation of CFC, the immunophenotype and the clonal cells(which had cytogenetic markers detected by FISH), was compared respectively. Results ¢Å The capacity of BMNC from 5 healthy donors to generate CFC remained unchanged in the CD4+CCR5+ T lymphocyte-depleted and lymphocyte-plused BMNC. In contrast, cultures initiated with CD4+CCR5+ T lymphocyte-depleted BMNC from patients with low-grade MDS exhibited significantly increased generation of CFC compared with the corresponding lymphocyte-plused cultures, but the lymphocyte-plused cultures had no generation of CFC. ¢Æ The number of CFU-E from the CD4+CCR5+ T lymphocyte-depleted BMNC from patients with low-grade MDS showed significantly correlation with the percentage of Th1 (r=0.52, p≤¼ 0.05), but had no correlation with the percentage of Tc1 and the rate of Th1/Th2 and Tc1/Tc2 (p >0.05); The number of CFC, CFU-G and CFU-GE had no correlation with the polarization of T lymphocyte (P >0.05). ¢Ç The percentage of CD34 in bone nucleated cells of low-grade MDS was higher than that in healthy donors(1.8% vs. 1.0%, P >0.05), that of CD33 in nucleated cells of low-grade MDS was significantly higher than that in healthy donors[(20.3±5.8)% vs.(13.8±1.8)%(P≤¼0.05)], and that of CD13 in nucleated cells of low-grade MDS was significantly higher than that in healthy donors[(21.1±6.4)% vs. (11.6±1.8)%(p<0.05)]. After cultivation, the percentage of CD34 in low-grade MDS nucleated cells decreased to 1.4%(P >0.05), that of CD33 decreased to (12.1±3.7)%(p<0.05), and that of CD13 decreased to (17.1±5.4)%(p<0.05), but the percentage of CD34, CD33 and CD13 had no significantly changed in healthy donors between pre-culture and post-culture. ¢È FISH analysis in 6 patients revealed that +8 clone was increased(from 51% to 61%), but 20q- and -7 clone cell had no significantly changed. Conclusion In certain subtypes of MDS, selectedly removement of autologous activated CD4T cells can increase the generation of colony-forming-cells(CFC) in vitro, and improve the differentiation of MDS medullary system, but the increased CFC consisting of residual normal hemopoiesis or conal hemopoiesis were still unconcluded.

scholarly journals Glycogen Synthase Kinase-3β Facilitates Cytokine Production in 12-O-Tetradecanoylphorbol-13-Acetate/Ionomycin-Activated Human CD4+ T Lymphocytes

Cells ◽  
2020 ◽  
Vol 9 (6) ◽  
pp. 1424
Author(s):  
Cheng-Chieh Tsai ◽  
Chin-Kun Tsai ◽  
Po-Chun Tseng ◽  
Chiou-Feng Lin ◽  
Chia-Ling Chen
Keyword(s):  
T Lymphocytes ◽  
T Lymphocyte ◽  
Cytokine Production ◽  
Nuclear Translocation ◽  
Glycogen Synthase ◽  
Interleukin 2 ◽  
Glycogen Synthase Kinase ◽  
Tyrosine Kinase 2 ◽  
Gsk 3Β

Cytokines are the major immune regulators secreted from activated CD4+ T lymphocytes that activate adaptive immunity to eradicate nonself cells, including pathogens, tumors, and allografts. The regulation of glycogen synthase kinase (GSK)-3β, a serine/threonine kinase, controls cytokine production by regulating transcription factors. The artificial in vitro activation of CD4+ T lymphocytes by a combination of 12-O-tetradecanoylphorbol-13-acetate and ionomycin, the so-called T/I model, led to an inducible production of cytokines, such as interferon-γ, tumor necrosis factor-α, and interleukin-2. As demonstrated by the approaches of pharmacological targeting and genetic knockdown of GSK-3β, T/I treatment effectively caused GSK-3β activation followed by GSK-3β-regulated cytokine production. In contrast, pharmacological inhibition of the proline-rich tyrosine kinase 2 and calcineurin signaling pathways blocked cytokine production, probably by deactivating GSK-3β. The blockade of GSK-3β led to the inhibition of the nuclear translocation of T-bet, a vital transcription factor of T lymphocyte cytokines. In a mouse model, treatment with the GSK-3β inhibitor 6-bromoindirubin-3’-oxime significantly inhibited T/I-induced mortality and serum cytokine levels. In summary, targeting GSK-3β effectively inhibits CD4+ T lymphocyte activation and cytokine production.

scholarly journals Effect of Coexpression of Interleukin-2 by Recombinant Respiratory Syncytial Virus on Virus Replication, Immunogenicity, and Production of Other Cytokines

2000 ◽  
Vol 74 (15) ◽  
pp. 7151-7157 ◽  
Author(s):  
Alexander Bukreyev ◽  
Stephen S. Whitehead ◽  
Calman Prussin ◽  
Brian R. Murphy ◽  
Peter L. Collins
Keyword(s):  
Respiratory Syncytial Virus ◽  
Mononuclear Cells ◽  
Protective Efficacy ◽  
Interleukin 2 ◽  
Cytokine Mrna ◽  
Virus Growth ◽  
Ifn Γ ◽  
Syncytial Virus

ABSTRACT We constructed rRSV/mIL-2, a recombinant respiratory syncytial virus (rRSV) containing the coding sequence of murine interleukin-2 (mIL-2) in a transcription cassette inserted into the G-F intergenic region. The recovered virus (rRSV/mIL-2) expressed high levels (up to 2.8 μg/ml) of mIL-2 in cell culture. Replication of rRSV/mIL-2 in vitro was reduced up to 13.6-fold from that of wild-type (wt) rRSV, an effect that was due to the presence of the foreign insert but was not specific to mIL-2. Replication of the rRSV/mIL-2 virus in the upper and lower respiratory tracts of BALB/c mice was reduced up to 6.3-fold, an effect that was specific to mIL-2. The antibody response, including the levels of RSV-specific serum immunoglobulin G1 (IgG1), IgG2a, IgA, and total IgG, and the level of protective efficacy against wt RSV challenge were not significantly different from those of wt rRSV. Analysis of total pulmonary cytokine mRNA isolated 1 and 4 days following infection with rRSV/mIL-2 revealed elevated levels of mRNA for IL-2, gamma interferon (IFN-γ), IL-4, IL-5, IL-6, IL-10, IL-13, and IL-12 p40 compared to those for wt rRSV. Flow cytometry of total pulmonary mononuclear cells isolated 10 days following infection with rRSV/mIL-2 revealed increased levels of CD4+ T lymphocytes expressing either IFN-γ or IL-4 compared to those of wt rRSV. These elevations in cytokine mRNA or cytokine-expressing CD4+cells relative to those of wt rRSV-primed animals were not observed following challenge with wt RSV on day 28. Thus, the expression of mIL-2 by rRSV was associated with a modest attenuation of virus growth in vivo, induction of serum antibodies at levels comparable to that of wt rRSV, and transient increases in both the Th1 and Th2 CD4+ lymphocytes and cytokine mRNAs compared to those of wt rRSV.

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 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.

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