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Adoptive transfer of allergen-specific CD4+ T cells induces airway inflammation and hyperresponsiveness in brown-Norway rats.

https://arctichealth.org/en/permalink/ahliterature57604
Source
Immunology. 1997 Jun;91(2):176-85
Publication Type
Article
Date
Jun-1997
Author
A. Haczku
P. Macary
T J Huang
H. Tsukagoshi
P J Barnes
A B Kay
D M Kemeny
K F Chung
R. Moqbel
Author Affiliation
Department of Allergy and Clinical Immunology, Guy's Hospital, London, UK.
Source
Immunology. 1997 Jun;91(2):176-85
Date
Jun-1997
Language
English
Publication Type
Article
Keywords
Adoptive Transfer
Animals
Bronchial Hyperreactivity - immunology
Bronchoalveolar Lavage Fluid - immunology
CD4-Positive T-Lymphocytes - immunology - transplantation
CD8-Positive T-Lymphocytes - immunology - transplantation
Cell Culture Techniques
Cell Division - immunology
Eosinophils - immunology
Leukocyte Count
Lymphocyte Transfusion
Male
Rats
Rats, Inbred BN
Research Support, Non-U.S. Gov't
Spleen - immunology
Abstract
Following allergen exposure, sensitized Brown-Norway rats develop airway hyperresponsiveness (AHR) and eosinophilic inflammation together with an increase in activated T cells (CD25+) in the airways. We tested the hypothesis that CD4+ T cells are involved directly in the acquisition of AHR. Spleen T cells from animals that were injected intraperitoneally on three consecutive days with ovalbumin/Al(OH)3, showed a dose-dependent proliferative response in vitro to ovalbumin, but not to bovine serum albumin, as measured by [3H]thymidine uptake. For total T-cell transfer, spleen cells obtained from donor rats 4 days after sensitization were depleted of adherent cells by a nylon wool column separation. CD4+ and CD8+ T cells were purified by immunomagnetic beads cell separation. Recipient naive rats were injected intravenously with 50 x 10(6) total T cells, 20 x 10(6) and 5 x 10(6) CD4+ cells, and 5 x 10(6) CD8+ cells, and were exposed to ovalbumin aerosol 24 hr afterwards. After a further 24 hr, airway responsiveness to acetylcholine (ACh) was measured and provocative concentration (PC) values PC100, PC200 and PC300) (the ACh concentration needed to achieve 100, 200 and 300% increase in lung resistance above baseline) were calculated. Airway responsiveness was significantly increased in recipients of sensitized total T cells compared with recipients of cells from saline-injected donor rats (P
PubMed ID
9227314 View in PubMed
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Allergen-specific Th1 cells counteract efferent Th2 cell-dependent bronchial hyperresponsiveness and eosinophilic inflammation partly via IFN-gamma.

https://arctichealth.org/en/permalink/ahliterature15527
Source
J Immunol. 2001 Jan 1;166(1):207-17
Publication Type
Article
Date
Jan-1-2001
Author
T J Huang
P A MacAry
P. Eynott
A. Moussavi
K C Daniel
P W Askenase
D M Kemeny
K F Chung
Author Affiliation
Thoracic Medicine, National Heart and Lung Institute, Imperial College School of Medicine, London, United Kingdom.
Source
J Immunol. 2001 Jan 1;166(1):207-17
Date
Jan-1-2001
Language
English
Publication Type
Article
Keywords
Administration, Inhalation
Adoptive Transfer
Allergens - administration & dosage - immunology
Animals
Antibodies, Monoclonal - administration & dosage
Bronchial Hyperreactivity - immunology - pathology - prevention & control
Bronchoalveolar Lavage Fluid - immunology
Cell Line
Epitopes, T-Lymphocyte - administration & dosage - immunology
Inflammation - immunology - pathology - prevention & control
Injections, Intravenous
Interferon Type II - immunology - physiology
Interleukin-4 - antagonists & inhibitors - genetics
Lung - cytology - immunology
Male
Ovalbumin - administration & dosage - immunology
Pulmonary Eosinophilia - immunology - pathology - prevention & control
RNA, Messenger - antagonists & inhibitors
Rats
Rats, Inbred BN
Research Support, Non-U.S. Gov't
Th1 Cells - immunology - transplantation
Th2 Cells - immunology - transplantation
Abstract
Th2 T cell immune-driven inflammation plays an important role in allergic asthma. We studied the effect of counterbalancing Th1 T cells in an asthma model in Brown Norway rats that favors Th2 responses. Rats received i.v. transfers of syngeneic allergen-specific Th1 or Th2 cells, 24 h before aerosol exposure to allergen, and were studied 18-24 h later. Adoptive transfer of OVA-specific Th2 cells, but not Th1 cells, and OVA, but not BSA exposure, induced bronchial hyperresponsiveness (BHR) to acetylcholine and eosinophilia in a cell number-dependent manner. Importantly, cotransfer of OVA-specific Th1 cells dose-dependently reversed BHR and bronchoalveolar lavage (BAL) eosinophilia, but not mucosal eosinophilia. OVA-specific Th1 cells transferred alone induced mucosal eosinophilia, but neither BHR nor BAL eosinophilia. Th1 suppression of BHR and BAL eosinophilia was allergen specific, since cotransfer of BSA-specific Th1 cells with the OVA-specific Th2 cells was not inhibitory when OVA aerosol alone was used, but was suppressive with OVA and BSA challenge. Furthermore, recipients of Th1 cells alone had increased gene expression for IFN-gamma in the lungs, while those receiving Th2 cells alone showed increased IL-4 mRNA. Importantly, induction of these Th2 cytokines was inhibited in recipients of combined Th1 and Th2 cells. Anti-IFN-gamma treatment attenuated the down-regulatory effect of Th1 cells. Allergen-specific Th1 cells down-regulate efferent Th2 cytokine-dependent BHR and BAL eosinophilia in an asthma model via mechanisms that depend on IFN-gamma. Therapy designed to control the efferent phase of established asthma by augmenting down-regulatory Th1 counterbalancing mechanisms should be effective.
PubMed ID
11123294 View in PubMed
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Effect of CD8+ T-cell depletion on bronchial hyper-responsiveness and inflammation in sensitized and allergen-exposed Brown-Norway rats.

https://arctichealth.org/en/permalink/ahliterature15670
Source
Immunology. 1999 Mar;96(3):416-23
Publication Type
Article
Date
Mar-1999
Author
T J Huang
P A MacAry
D M Kemeny
K F Chung
Author Affiliation
Thoracic Medicine, Chang Gung Memorial Hospital, Keelung Branch, Taiwan, China; Thoracic Medicine, National Heart & Lung Institute, Imperial College School of Medicine, London, UK.
Source
Immunology. 1999 Mar;96(3):416-23
Date
Mar-1999
Language
English
Publication Type
Article
Keywords
Acetylcholine - immunology
Allergens - immunology
Animals
Antibodies, Monoclonal - immunology
Asthma - immunology - physiopathology
Blotting, Southern
Bronchial Hyperreactivity - immunology
Bronchoalveolar Lavage Fluid - immunology
CD8-Positive T-Lymphocytes - immunology
Cytokines - biosynthesis
Immunoenzyme Techniques
Lung - immunology
Lymphocyte Count
Male
Mice
Ovalbumin - immunology
Rats
Rats, Inbred BN
Reverse Transcriptase Polymerase Chain Reaction
Vasodilator Agents - immunology
Abstract
We examined the role of CD8+ T cells in a Brown-Norway rat model of asthma, using a monoclonal antibody to deplete CD8+ T cells. Ovalbumin (OA)-sensitized animals were given anti-CD8 antibody (0.5 mg/rat) intravenously 1 week prior to exposure to 1% OA aerosol and were studied 18-24 hr after aerosol exposure. Following administration of anti-CD8 antibody, CD8+ cells were reduced to
PubMed ID
10233723 View in PubMed
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Involvement of cysteinyl leukotrienes in airway smooth muscle cell DNA synthesis after repeated allergen exposure in sensitized Brown Norway rats.

https://arctichealth.org/en/permalink/ahliterature15646
Source
Br J Pharmacol. 1999 Jul;127(5):1151-8
Publication Type
Article
Date
Jul-1999
Author
M. Salmon
D A Walsh
T J Huang
P J Barnes
T B Leonard
D W Hay
K F Chung
Author Affiliation
Thoracic Medicine, Imperial College School of Medicine at the National Heart and Lung Institute, London, UK.
Source
Br J Pharmacol. 1999 Jul;127(5):1151-8
Date
Jul-1999
Language
English
Publication Type
Article
Keywords
Acetylcholine - pharmacology
Allergens - immunology
Animals
Arachidonate 5-Lipoxygenase - physiology
Bronchi - drug effects - metabolism
Cell Count
Cysteine - physiology
DNA - biosynthesis
Eosinophils - physiology
Leukotrienes - physiology
Male
Muscle, Smooth - metabolism
Rats
Rats, Inbred BN
Research Support, Non-U.S. Gov't
Abstract
Airway smooth muscle thickening is a characteristic feature of airway wall remodelling in chronic asthma. We have investigated the role of the leukotrienes in airway smooth muscle (ASM) and epithelial cell DNA synthesis and ASM thickening following repeated allergen exposure in Brown Norway rats sensitized to ovalbumin. There was a 3 fold increase in ASM cell DNA synthesis, as measured by percentage bromodeoxyuridine (BrdU) incorporation, in repeatedly ovalbumin-exposed (4.1%, 3.6-4.6; mean, 95% c.i.) compared to chronically saline-exposed rats (1.3%, 0.6-2.1; P
PubMed ID
10455261 View in PubMed
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A novel transcription factor inhibitor, SP100030, inhibits cytokine gene expression, but not airway eosinophilia or hyperresponsiveness in sensitized and allergen-exposed rat.

https://arctichealth.org/en/permalink/ahliterature15448
Source
Br J Pharmacol. 2001 Nov;134(5):1029-36
Publication Type
Article
Date
Nov-2001
Author
T J Huang
I M Adcock
K F Chung
Author Affiliation
Thoracic Medicine, Chang Gung Memorial Hospital, Keelung Branch, Taiwan, Republic of China.
Source
Br J Pharmacol. 2001 Nov;134(5):1029-36
Date
Nov-2001
Language
English
Publication Type
Article
Keywords
Allergens - immunology
Animals
Antigens, CD2 - analysis
Antigens, CD4 - analysis
Antigens, CD8 - analysis
Blotting, Western
Bronchial Hyperreactivity - genetics - immunology - prevention & control
Bronchoalveolar Lavage Fluid - cytology
Cytokines - genetics
Eosinophils - cytology - drug effects - immunology
Gene Expression Regulation - drug effects
Immunohistochemistry
Immunosuppressive Agents - pharmacology
Interferon Type II - genetics
Interleukin-10 - genetics
Interleukin-2 - genetics
Interleukin-4 - genetics
Interleukin-5 - genetics
Lung - drug effects - metabolism
Lymphocytes - cytology - drug effects - immunology
Macrophages - cytology - drug effects - immunology
Male
NF-kappa B - antagonists & inhibitors
Neutrophils - cytology - drug effects - immunology
Organic Chemicals
Ovalbumin - immunology
Proto-Oncogene Proteins c-jun - drug effects - metabolism
Pulmonary Eosinophilia - genetics - immunology - prevention & control
RNA, Messenger - drug effects - genetics - metabolism
Rats
Rats, Inbred BN
Respiratory Mucosa - drug effects - immunology - pathology
Specific Pathogen-Free Organisms
Transcription Factor AP-1 - antagonists & inhibitors
Transcription Factors - antagonists & inhibitors
Abstract
1. We examined the effect of SP100030, a novel inhibitor of activator protein-1 (AP-1) and nuclear factor (NF)-kappa B transcription factors, in a rat model of asthma. 2. Sensitized Brown-Norway rats were treated with SP100030 (20 mg kg(-1) day(-1) for 3 days) intraperitoneally prior to allergen challenge. Allergen exposure of sensitized rats induced bronchial hyperresponsiveness (BHR), accumulation of inflammatory cells in bronchoalveolar lavage (BAL) fluid, and also an increase in eosinophils and CD2(+), CD4(+) and CD8(+) T-cells in the airways together with mRNA expression for IL-2, IL-4, IL-5, IL-10, and IFN-gamma. 3. Pre-treatment with SP100030 inhibited BAL lymphocyte influx (P
PubMed ID
11682451 View in PubMed
Less detail