만성 알레르기 기도염증에서 CD8(+) T세포의 역할
Role of CD8(+) T Cell in Chronic Allergic Airway Inflammation
2
조회
0
다운로드
0
인용
0
참고문헌
키워드
초록
Purpose:Asthma is a complex disease that is characterized by airway hyperresponsiveness (AHR), reversible airway obstruction, and inflammation, marked mainly by eosinophilic infiltration. The bulk of the evidence identifies αCD4(+) TH2 cells as having a pivotal role in mediating the inflammation that is central to asthma but The role of CD8(+) T cells in the development of allergic airway disease is still controversial. The purpose of this study was to investigate the role of CD8(+) T cells in the development of AHR and airway inflammation in mouse model of chronic asthma. Methods:Mice were sensitized to OVA by i.p. injection on day 1, 14 and then challenged by OVA intranasal instillation on days 27, 28, 29 47, 61, 73, 74 and then 75 days. Anti-CD8 antibody was administered to sensitized mice by i.v. injection 2h before second sensitization, day 27 and 73. In vivo airway responsiveness was measured by whole body plethysmography (Penh) to inhaled methacholine (MCh) on day 77. Lung eosinophilia, bronchoalveolar lavage fluid (BALF) cytokine levels were also assessed. Results:Sensitized and challenged mice showed significant airway eosinophilia and heightened AHR to methacholine when compared with nonsensitized animals. Administration of anti-CD8 antibody prevented both development of AHR as well as BALF eosinophilia. Treatment with anti-CD8 antibody also resulted in supression of IL-5 production in BALF. Conclusion:These results indicate that CD8 (+) T cell may have a potential role in the development of chronic allergic airway inflammation and development of allergen-induced airway responses in mouse model.
Abstract
Purpose:Asthma is a complex disease that is characterized by airway hyperresponsiveness (AHR), reversible airway obstruction, and inflammation, marked mainly by eosinophilic infiltration. The bulk of the evidence identifies αCD4(+) TH2 cells as having a pivotal role in mediating the inflammation that is central to asthma but The role of CD8(+) T cells in the development of allergic airway disease is still controversial. The purpose of this study was to investigate the role of CD8(+) T cells in the development of AHR and airway inflammation in mouse model of chronic asthma. Methods:Mice were sensitized to OVA by i.p. injection on day 1, 14 and then challenged by OVA intranasal instillation on days 27, 28, 29 47, 61, 73, 74 and then 75 days. Anti-CD8 antibody was administered to sensitized mice by i.v. injection 2h before second sensitization, day 27 and 73. In vivo airway responsiveness was measured by whole body plethysmography (Penh) to inhaled methacholine (MCh) on day 77. Lung eosinophilia, bronchoalveolar lavage fluid (BALF) cytokine levels were also assessed. Results:Sensitized and challenged mice showed significant airway eosinophilia and heightened AHR to methacholine when compared with nonsensitized animals. Administration of anti-CD8 antibody prevented both development of AHR as well as BALF eosinophilia. Treatment with anti-CD8 antibody also resulted in supression of IL-5 production in BALF. Conclusion:These results indicate that CD8 (+) T cell may have a potential role in the development of chronic allergic airway inflammation and development of allergen-induced airway responses in mouse model.
참고문헌 (28)
- Lee NA, "Pulmonary T cells and eosinophils: co-conspirators or independent triggers of allergic respiratory pathology", J Allergy Clin Immunol, 107, pp.945~957 (2001)
- Busse WW, "Mechanisms of persistent airway inflammation in asthma: a role for T cells and T-cell products", Am J Respir Crit Care Med, 152, pp.388~393 (1995)
- Cohn L, "IL-4-independent induction of airway hyperresponsiveness by Th2, but not Th1, cells", J Immunol, 161, pp.3813~3816 (1998)
- Gavett SH, "Depletion of murine CD4+T lymphocytes prevents antigen-induced airway hyperreactivity and pulmonary eosinophilia", Am J Respir Cell Mol Biol, 10, pp.587~593 (1994)
- Grunig G, "Requirement for IL-13 independently of IL-4 in experimental asthma", Science, 282, pp.2261~2267 (1998)
- McKenzie GJ, "Impaired development of Th2 cells in IL-13-deficient mice", Immunity, 9, pp.423~432 (1998)
- Robinson DS, "Predominant TH2-like bronchoalveolar T-lymphocyte population in atopic asthma", N Engl J Med, 326, pp.298~304 (1992)
- Haczku A, "Adoptive transfer of allergen-specific CD4+ T cells induces airway inflammation and hyperresponsiveness in Brown-Norway rats", Immunology, 91, pp.176~183 (1997)
- Watanabe A, "Transfer of allergic airway responses with antigen-primed CD4+ but not CD8+ Tcells in Brown-Norway rats", J Clin Invest, 96, pp.1303~1310 (1995)
- Hogan SP, "Interleukin-5-producing CD4+ T cells play a pivotal role in aeroallergen-induced eosinophilia, bronchial hyperreactivity, and lung damage in mice", Am J Respir Crit Care Med, 157, pp.210~218 (1998)
- Cohn L, "Induction of airway mucus production by T helper 2 (Th2) cells: a critical role for interleukin 4 in cell recruitment but not mucus production", J Exp Med, 186, pp.1737~1742 (1997)
- Kaminuma O, "Successful transfer of late phase eosinophil infiltration in the lung by infusion of helper T cell clones", Am J Respir Cell Mol Biol, 16, pp.448~454 (1997)
- Robinson DS, "Predominant Th2-like bronchoalveolar T-lymphocyte population in atopic asthma", N Engl J Med, 326, pp.298~304 (1992)
- Ray A, "Th2 cells and GATA-3 in asthma: new insights into the regulation of airway inflammation", J Clin Invest, 104, pp.985~993 (1999)
- Rha YH, "Role of CD8(+) cellss in airway inflammation and hyperersponsiveness", Pediatr Allergy Respir Dis (Korea), 15, pp.160~169 (2005)
- Corrigan CJ, "Peripheral blood CD4, but not CD8 T lymphocytes in patients with exacerbation of asthma transcribe and translate messenger RNA encoding cytokines which prolong eosinophil survival in the context of a Th2-type pattern: Effect of glucocorticoid therapy", Am J Respir Cell Mol Biol, 12, pp.567~578 (1995)
- Haczku A, "Inhibition of re-expression of surface CD4, but not CD8, on activated human T-lymphocytes by the immunosuppressive drugs dexamethasone and cyclosporine A: Correlation with inhibition of proliferation", Int J immunopharmacol, 18, pp.45~52 (1996)
- Finkelman FD, "IL-4 is required to generate and sustain in vivo IgE responses", J Immunol, 141, pp.2335~2341 (1988)
- Cho SH, "Increased interleukin-4, 5 and interferon-(gamma) in airway CD4+ and CD8+ T cells in atopic asthma", Am J Respir Crit Care Med, 171, pp.224~230 (2005)
- Till S, "Secretion of eosinophil- active cytokines interleukin-5, granulocyte", macrophage colony stimulating factor and interleukin-3 by bronchoalveolar lavage CD4+ and CD8+ T cell lines in atopic asthmatics, and atopic and non-atopic controls, 1995, pp.25, 2727~2731
- Ying S, "Expression of IL-4 and IL-5 mRNA and protein product by CD4+ and CD8+ T-cells, eosinophils and mast cells in bronchial biopsies obtained from atopic and non-atopic(intrinsic) asthmatics", J Immunol, 158, pp.3539~3544 (1997)
- Canonica GW, "Imbalances of T cell subpopulations in patients with atopic diseases and effect of specific immunotherapy", J Immunol, 123, pp.2669~2672 (1979)
- Walker C, "Allergic and nonallergic asthmatics have distinct patterns of T cell activation and cytokine production in peripheral blood and bronchoalveolar lavage", Am Rev Respir Dis, 146, pp.109~115 (1992)
- Faure MR, "Decreased levels of T cells and cells with suppressor T cell phenotype as difined by specific bonoclonal antibodies in patients with atopic dermatitis", Clin Exp Dermatol, 7, pp.513~518 (1982)
- O'Sullivan S, "Activated, cytotoxic CD8+ T lymphocytes contribute to the pathology of asthma death", Am J Respir Crit Care Med, 164, pp.560~567 (2001)
- Kanehiro A, "Inhibition of phosphodiesterase 4 attenuates airway hyperresponsiveness and airway inflammation in model ofsecondary allergen challenge", Am J Respir CirtCare Med, 16, pp.173~184 (2001)
- Bousquet J, "Eosinophilic inflammation in asthma", N Engl J Med, 323, pp.1033~1039 (1990)
- Sedgwick JD, "Suppression of IgE responses in inbred rats by repeated respiratory tract exposure to antigen: Responder phenotype influences isotype specificity of induced tolerance", Eur J Immunol, 14, pp.893~897 (1984)
