CD8+T lymphocytes in lung tissue from patients with idiopathic pulmonary fibrosis

Daniil Zoe, Kitsanta Panagiota, Kapotsis George, Mathioudaki Maria, Karatza Marilena, Roussos Charis, Kollintza Androniki, Milic-Emili Joseph, Papiris

Description

Several studies have implicated a role of inflammation in the pathogenesis of lung damage in idiopathic pulmonary fibrosis (IPF). Parenchymal lung damage leads to defects in mechanics and gas exchange and clinically manifests with exertional dyspnea. Investigations of inflammatory cells in IPF have shown that eosinophils, neutrophils and CD 8+ TLs may be associated with worse prognosis. We wished to investigate by quantitative immunohistochemistry infiltrating macrophages, neutrophils and T lymphocytes (TLs) subpopulations (CD 3+ , CD 4+ and CD 8+ ) in lung tissue of patients with IPF and their correlation with lung function indices and grade of dyspnoea. Methods Surgical biopsies of 12 patients with IPF were immunohistochemically stained with mouse monoclonal antibodies (anti-CD 68 for macrophages, anti-elastase for neutrophils, and anti-CD 3 , anti-CD 4 , anti-CD 8 for CD 3+ TLs, CD 4+ TLs, and CD 8+ TLs respectively). The number of positively stained cells was determined by observer-interactive computerized image analysis (SAMBA microscopic image processor). Cell numbers were expressed in percentage of immunopositive nuclear surface in relation to the total nuclear surface of infiltrative cells within the tissue (labeling Index). Correlations were performed between cell numbers and physiological indices [FEV 1 , FVC, TLC, D LCO, PaO 2 , PaCO 2 and P(A-a)O 2 )] as well as dyspnoea scores assessed by the Medical Research Council (MRC) scale. Results Elastase positive cells accounted for the 7.04% ± 1.1 of total cells, CD 68+ cells for the 16.6% ± 2, CD 3+ TLs for the 28.8% ± 7, CD 4+ TLs for the 14.5 ± 4 and CD 8+ TLs for the 13.8 ± 4. CD 8+ TLs correlated inversely with FVC % predicted (r s = -0.67, p = 0.01), TLC % predicted (r s = -0.68, p = 0.01), DLCO % predicted (r s = -0.61, p = 0.04), and PaO 2 (r s = -0.60, p = 0.04). Positive correlations were found between CD 8+ TLs and P(A-a)O 2 (r s = 0.65, p = 0.02) and CD 8+ TLs and MRC score (r s = 0.63, p = 0.02). Additionally, CD 68+ cells presented negative correlations with both FVC % predicted (r s = -0.80, p = 0.002) and FEV 1 % predicted (r s = -0.68, p = 0.01). Conclusion In UIP/IPF tissue infiltrating mononuclear cells and especially CD 8+ TLs are associated with the grade of dyspnoea and functional parameters of disease severity implicating that they might play a role in its pathogenesis.

Informations

• Publié par: biomed
• Publié le: 01 janvier 2005
• Nombre de lectures: 13
• Langue: English

Extrait

Respiratory Research

BioMedCentral

Open Access Research CD Tlymphocytes in lung tissue from patients with idiopathic 8+ pulmonary fibrosis 1 21 2 Zoe Daniil, Panagiota Kitsanta, George Kapotsis, Maria Mathioudaki, 1 34 Androniki Kollintza, Marilena Karatza, Joseph MilicEmili, 1 1 Charis Roussosand Spyros A Papiris*

1 Address: Departmentof Critical Care and Pulmonary Services, National and Capodistrian University of Athens, "Evangelismos" Hospital, Athens, 2 3 Greece, PathologyDepartment, "Evangelismos" Hospital, Athens, Greece,Hematology Department, "Evangelismos" Hospital, Athens, Greece 4 and MeakinsCristieLaboratories, McGill University, Montreal, Quebec, Canada Email: Zoe Daniil  [e-mail]; Panagiota Kitsanta  [e-mail]; George Kapotsis  [e-mail]; Maria Mathioudaki  [e-mail]; Androniki Kollintza  [e-mail]; Marilena Karatza  [e-mail]; Joseph MilicEmili  Joseph.Milic[e-mail]; Charis Roussos  [e-mail]; Spyros A Papiris*  [e-mail] * Corresponding author

Published: 24 July 2005Received: 26 May 2005 Accepted: 24 July 2005 Respiratory Research2005,6:81 doi:10.1186/1465-9921-6-81 This article is available from: http://respiratory-research.com/content/6/1/81 © 2005 Daniil et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract Background:Several studies have implicated a role of inflammation in the pathogenesis of lung damage in idiopathic pulmonary fibrosis (IPF). Parenchymal lung damage leads to defects in mechanics and gas exchange and clinically manifests with exertional dyspnea. Investigations of inflammatory cells in IPF have shown that eosinophils, neutrophils and CD 8+ TLs may be associated with worse prognosis. We wished to investigate by quantitative immunohistochemistry infiltrating macrophages, neutrophils and T lymphocytes (TLs) subpopulations (CD, CDand CD) in lung tissue of patients with 3+ 4+8+ IPF and their correlation with lung function indices and grade of dyspnoea. Methods:Surgical biopsies of 12 patients with IPF were immunohistochemically stained with mouse monoclonal antibodies (anti-CDfor macrophages, anti-elastase for neutrophils, and anti-CD , anti-CD , anti-CDfor CDTLs, 68 34 83+ CD TLs,and CDTLs respectively). The number of positively stained cells was determined by observer-interactive 4+ 8+ computerized image analysis (SAMBA microscopic image processor). Cell numbers were expressed in percentage of immunopositive nuclear surface in relation to the total nuclear surface of infiltrative cells within the tissue (labeling Index). Correlations were performed between cell numbers and physiological indices [FEV , FVC, TLC,DLCO, PaO , PaCO 1 22 and P(A-a)O )] as well as dyspnoea scores assessed by the Medical Research Council (MRC) scale. 2 Results:Elastase positive cells accounted for the 7.04% ± 1.1 of total cells, CDcells for the 16.6% ± 2, CDTLs for 68+ 3+ the 28.8% ± 7, CDTLs for the 14.5 ± 4 and CDTLs for the 13.8 ± 4. CDTLs correlated inversely with FVC % 4+ 8+8+ predicted (r= -0.67, p = 0.01), TLC % predicted (r= -0.68, p = 0.01), DLCO % predicted (r= -0.61, p = 0.04), and s ss PaO (r =-0.60, p = 0.04). Positive correlations were found between CDTLs and P(A-a)O(r =0.65, p = 0.02) and 2 s8+ 2s CD TLsand MRC score (r= 0.63, p = 0.02). Additionally, CDcells presented negative correlations with both FVC 8+ s68+ % predicted (r= -0.80, p = 0.002) and FEV% predicted (r= -0.68, p = 0.01). s 1s Conclusion:In UIP/IPF tissue infiltrating mononuclear cells and especially CDTLs are associated with the grade of 8+ dyspnoea and functional parameters of disease severity implicating that they might play a role in its pathogenesis.

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