CD25+ Natural Regulatory T Cells Are Critical in Limiting Innate and Adaptive Immunity and Resolving Disease following Respiratory Syncytial Virus Infection

ABSTRACT Regulatory CD4+ T cells have been shown to be important in limiting immune responses, but their role in respiratory viral infections has received little attention. Here we observed that following respiratory syncytial virus (RSV) infection, CD4+ Foxp3+ CD25+ natural regulatory T-cell numbers increased in the bronchoalveolar lavage fluid, lung, mediastinal lymph nodes, and spleen. The depletion of CD25+ natural regulatory T cells prior to RSV infection led to enhanced weight loss with delayed recovery that was surprisingly accompanied by increased numbers of activated natural killer cells in the lung and bronchoalveolar lavage fluid on day 8 postinfection. Increased numbers of neutrophils were also detected within the bronchoalveolar lavage fluid and correlated with elevated levels of myeloperoxidase as well as interleukin-6 (IL-6) and gamma interferon (IFN-γ). CD25+ natural regulatory T-cell depletion also led to enhanced numbers of proinflammatory T cells producing IFN-γ and tumor necrosis factor alpha (TNF-α) in the lung. Despite these increases in inflammatory responses and disease severity, the viral load was unaltered. This work highlights a critical role for natural regulatory T cells in regulating the adaptive and innate immune responses during the later stages of lung viral infections.

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CD25+ Regulatory T Cells in Bronchoalveolar Lavage Fluid Are Associated with Lung Allograft Rejection

The Journal of Heart and Lung Transplantation ◽

10.1016/j.healun.2014.01.805 ◽

2014 ◽

Vol 33 (4) ◽

pp. S300 ◽

Cited By ~ 1

Author(s):

J.R. Greenland ◽

C.M. Wong ◽

R. Ahuja ◽

M. Gottschall ◽

N.N. Trivedi ◽

...

Keyword(s):

T Cells ◽

Regulatory T Cells ◽

Bronchoalveolar Lavage ◽

Allograft Rejection ◽

Bronchoalveolar Lavage Fluid ◽

Lavage Fluid

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407 Regulatory T Cells in Transbronchial Biopsies Compared with FoxP3 mRNA Level in Bronchoalveolar Lavage Fluid

The Journal of Heart and Lung Transplantation ◽

10.1016/j.healun.2012.01.417 ◽

2012 ◽

Vol 31 (4) ◽

pp. S144

Author(s):

D. Krustrup ◽

C.B. Madsen ◽

M. Iversen ◽

C.B. Andersen

Keyword(s):

T Cells ◽

Regulatory T Cells ◽

Bronchoalveolar Lavage ◽

Bronchoalveolar Lavage Fluid ◽

Mrna Level ◽

Lavage Fluid ◽

Foxp3 Mrna

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CD4+/CD25 high /FoxP3+/CD127− regulatory T cells in bronchoalveolar lavage fluid of lung cancer patients

Human Immunology ◽

10.1016/j.humimm.2016.07.235 ◽

2016 ◽

Vol 77 (10) ◽

pp. 912-915 ◽

Cited By ~ 8

Author(s):

Iwona Osińska ◽

Anna Stelmaszczyk-Emmel ◽

Małgorzata Polubiec-Kownacka ◽

Dariusz Dziedzic ◽

Joanna Domagała-Kulawik

Keyword(s):

Lung Cancer ◽

T Cells ◽

Regulatory T Cells ◽

Bronchoalveolar Lavage ◽

Cancer Patients ◽

Bronchoalveolar Lavage Fluid ◽

Lavage Fluid ◽

Lung Cancer Patients

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The number of regulatory T cells in transbronchial lung allograft biopsies is related to FoxP3 mRNA levels in bronchoalveolar lavage fluid and to the degree of acute cellular rejection

Transplant Immunology ◽

10.1016/j.trim.2013.08.002 ◽

2013 ◽

Vol 29 (1-4) ◽

pp. 71-75 ◽

Cited By ~ 9

Author(s):

Dorrit Krustrup ◽

Caroline B. Madsen ◽

Martin Iversen ◽

Lars Engelholm ◽

Lars P. Ryder ◽

...

Keyword(s):

T Cells ◽

Regulatory T Cells ◽

Bronchoalveolar Lavage ◽

Bronchoalveolar Lavage Fluid ◽

Lavage Fluid ◽

Acute Cellular Rejection ◽

Mrna Levels ◽

Foxp3 Mrna ◽

Cellular Rejection

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Adipose-Derived Stem Cells Ameliorate Allergic Airway Inflammation by Inducing Regulatory T Cells in a Mouse Model of Asthma

Mediators of Inflammation ◽

10.1155/2014/436476 ◽

2014 ◽

Vol 2014 ◽

pp. 1-12 ◽

Cited By ~ 34

Author(s):

Kyu-Sup Cho ◽

Mi-Kyung Park ◽

Shin-Ae Kang ◽

Hee-Young Park ◽

Sung-Lyong Hong ◽

...

Keyword(s):

Stem Cells ◽

T Cells ◽

Regulatory T Cells ◽

Bronchoalveolar Lavage ◽

Airway Inflammation ◽

Bronchoalveolar Lavage Fluid ◽

Immune Cell ◽

Allergic Airway Inflammation ◽

Lavage Fluid ◽

Th2 Cytokines

Although several studies have demonstrated that mesenchymal stem cells derived from adipose tissue (ASCs) can ameliorate allergic airway inflammation, the immunomodulatory mechanism of ASCs remains unclear. In this study, we investigated whether regulatory T cells (Tregs) induction is a potential mechanism in immunomodulatory effects of ASCs on allergic airway disease and how these induced Tregs orchestrate allergic inflammation. Intravenous administration of ASCs significantly reduced allergic symptoms and inhibited eosinophilic inflammation. Airway hyperresponsiveness, total immune cell and eosinophils in the bronchoalveolar lavage fluid, mucus production, and serum allergen-specific IgE and IgG1 were significantly reduced after ASCs administration. ASCs significantly inhibited Th2 cytokines (IL-4, IL-5, and IL-13) and enhanced Th1 cytokine (IFN-γ) and regulatory cytokines (IL-10 and TGF-β) in the bronchoalveolar lavage fluid and lung draining lymph nodes. Furthermore, levels of IDO, TGF-β, and PGE2were significantly increased after ASCs administration. Interestingly, this upregulation was accompanied by increased Treg populations. In conclusion, ASCs ameliorated allergic airway inflammation and improved lung function through the induction of Treg expansion. The induction of Treg by ASCs involves the secretion of soluble factors such as IDO, TGF-β, and PGE2and Treg might be involved in the downregulation of Th2 cytokines and upregulation of Th1 cytokines production.

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Evaluation of LBM415 (NVP PDF-713), a Novel Peptide Deformylase Inhibitor, for Treatment of Experimental Mycoplasma pneumoniae Pneumonia

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.49.10.4128-4136.2005 ◽

2005 ◽

Vol 49 (10) ◽

pp. 4128-4136 ◽

Cited By ~ 16

Author(s):

Monica Fonseca-Aten ◽

Christine M. Salvatore ◽

Asunción Mejías ◽

Ana M. Ríos ◽

Susana Chávez-Bueno ◽

...

Keyword(s):

Bronchoalveolar Lavage ◽

Mycoplasma Pneumoniae ◽

Bronchoalveolar Lavage Fluid ◽

Lavage Fluid ◽

Placebo Treatment ◽

Community Acquired Pneumonia ◽

Peptide Deformylase ◽

Necrosis Factor Alpha ◽

Days Of Therapy ◽

Ifn Γ

ABSTRACT Mycoplasma pneumoniae is a major cause of community-acquired pneumonia. We evaluated the efficacy of LBM415, a novel peptide deformylase inhibitor antimicrobial agent, for the treatment of M. pneumoniae pneumonia in a mouse model. Eight-week-old BALB/c mice were intranasally inoculated once with 107 CFU of M. pneumoniae. Groups of mice were treated with LBM415 (50 mg/kg of body weight) or placebo subcutaneously daily for 13 days, starting 24 h after inoculation. Groups of mice were evaluated at the baseline; at days of treatment 1, 3, 6, and 13; and at 7 days after treatment. The MIC of LBM415 against M. pneumoniae was <0.005 μg/ml. LBM415-treated mice had significantly lower bronchoalveolar lavage fluid M. pneumoniae concentrations than placebo-treated mice on days 6 and 13 of treatment. Compared with placebo treatment, therapy with LBM415 significantly decreased lung histopathology scores at days 3, 6, and 13 of treatment and at 7 days after treatment. Airway obstruction was significantly lower in LBM415-treated mice than in placebo-treated mice on days 1, 3, and 6 of treatment and after 7 days of therapy, while airway hyperresponsiveness was significantly lower only on day 3 of therapy. The bronchoalveolar lavage fluid concentrations of tumor necrosis factor alpha, gamma interferon (IFN-γ), interleukin-6 (IL-6), IL-12, KC (functional IL-8), monocyte chemotactic protein 1, macrophage inflammatory protein 1α, monokine induced by IFN-γ, and IFN-inducible protein 10 were significantly reduced in LBM415-treated mice compared with the levels in placebo-treated mice. There were no differences in the bronchoalveolar lavage fluid concentrations of granulocyte-macrophage colony-stimulating factor, IL-1β, IL-2, IL-4, IL-5, and IL-10 between the two groups of mice. LBM415 therapy had beneficial microbiologic, histologic, respiratory, and immunologic effects on acute murine M. pneumoniae pneumonia.

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Paeonol attenuates airway inflammation and hyperresponsiveness in a murine model of ovalbumin-induced asthma

Canadian Journal of Physiology and Pharmacology ◽

10.1139/y10-077 ◽

2010 ◽

Vol 88 (10) ◽

pp. 1010-1016 ◽

Cited By ~ 20

Author(s):

Qiang Du ◽

Gan-Zhu Feng ◽

Li Shen ◽

Jin Cui ◽

Jian-Kang Cai

Keyword(s):

Bronchoalveolar Lavage ◽

Airway Inflammation ◽

Bronchoalveolar Lavage Fluid ◽

Immunoglobulin E ◽

Therapeutic Potential ◽

Lavage Fluid ◽

Interleukin 4 ◽

Moutan Cortex ◽

Ifn Γ ◽

Anti Inflammatory

Paeonol, the main active component isolated from Moutan Cortex, possesses extensive pharmacological activities such as anti-inflammatory, anti-allergic, and immunoregulatory effects. In the present study, we examined the effects of paeonol on airway inflammation and hyperresponsiveness in a mouse model of allergic asthma. BALB/c mice sensitized and challenged with ovalbumin were administered paeonol intragastrically at a dose of 100 mg/kg daily. Paeonol significantly suppressed ovalbumin-induced airway hyperresponsiveness to acetylcholine chloride. Paeonol administration significantly inhibited the total inflammatory cell and eosinophil count in bronchoalveolar lavage fluid. Treatment with paeonol significantly enhanced IFN-γ levels and decreased interleukin-4 and interleukin-13 levels in bronchoalveolar lavage fluid and total immunoglobulin E levels in serum. Histological examination of lung tissue demonstrated that paeonol significantly attenuated allergen-induced lung eosinophilic inflammation and mucus-producing goblet cells in the airway. These data suggest that paeonol exhibits anti-inflammatory activity in allergic mice and may possess new therapeutic potential for the treatment of allergic bronchial asthma.

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NK T Cells Contribute to Expansion of CD8+ T Cells and Amplification of Antiviral Immune Responses to Respiratory Syncytial Virus

Journal of Virology ◽

10.1128/jvi.76.9.4294-4303.2002 ◽

2002 ◽

Vol 76 (9) ◽

pp. 4294-4303 ◽

Cited By ~ 130

Author(s):

Teresa R. Johnson ◽

Seokmann Hong ◽

Luc Van Kaer ◽

Yasuhiko Koezuka ◽

Barney S. Graham

Keyword(s):

T Cells ◽

Respiratory Syncytial Virus ◽

T Lymphocytes ◽

Immune Responses ◽

Natural Killer ◽

Viral Clearance ◽

Normal Numbers ◽

Nk T Cells ◽

Ifn Γ ◽

Syncytial Virus

ABSTRACT CD1d-deficient mice have normal numbers of T lymphocytes and natural killer cells but lack Vα14+ natural killer T cells. Respiratory syncytial virus (RSV) immunopathogenesis was evaluated in 129×C57BL/6, C57BL/6, and BALB/c CD1d−/− mice. CD8+ T lymphocytes were reduced in CD1d−/− mice of all strains, as shown by cell surface staining and major histocompatibility complex class I tetramer analysis, and resulted in strain-specific alterations in illness, viral clearance, and gamma interferon (IFN-γ) production. Transient activation of NK T cells in CD1d+/+ mice by α-GalCer resulted in reduced illness and delayed viral clearance. These data suggest that early IFN-γ production and efficient induction of CD8+-T-cell responses during primary RSV infection require CD1d-dependent events. We also tested the ability of α-GalCer as an adjuvant to modulate the type 2 immune responses induced by RSV glycoprotein G or formalin-inactivated RSV immunization. However, immunized CD1-deficient or α-GalCer-treated wild-type mice did not exhibit diminished disease following RSV challenge. Rather, some disease parameters, including cytokine production, eosinophilia, and viral clearance, were increased. These findings indicate that CD1d-dependent NK T cells play a role in expansion of CD8+ T cells and amplification of antiviral responses to RSV.

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