Implication of antigen-driven mechanisms in the pathogenesis of interstitial pneumonia associated with polymyositis
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1
International University of Health and Welfare Hospital, Division of Clinical Immunology & Rheumatology, Japan
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2
St. Luke's International Hospital, Division of Allergy & Rheumatology, Japan
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3
Dokkyo University School of Medicine, Department of Pulmonary Medicine and Clinical Immunology, Japan
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4
Wakayama Medical University, Laboratory of Immune Regulation, Japan
Objective:
Connective tissue diseases (CTDs) frequently involve the lung. Polymyositis (PM) is a major CTD characterized by chronic inflammatory lesions of muscle and other organs, including critical pulmonary involvement. Interstitial lung diseases, mainly interstitial pneumonia (IP), have been recognized in 30% - 70% of PM patients and have a poor prognosis. While the presence of myositis-specific autoantibodies suggests an autoimmune etiology of PM, the pathogenesis of PM-associated IP remains unclear. The aim of this study was to elucidate the role of T cells in this pulmonary complication.
Methods:
We took advantage of a rare opportunity to carefully study the cases of earliest-stage IP associated with PM by utilizing lung biopsy tissue. We characterized the phenotype of lung-infiltrating lymphocytes from lung biopsy specimens obatained by video-assisted thoracoscopy, and analyzed T-cell receptor a-chain (TCR Va) and TCR b-chain (TCR Vb) variable region repertoires of T-cells infiltrating the lung tissues using a validated adaptor ligation polymerase chain reaction (PCR)-based microplate hybridization assay, comparing these to peripheral blood lymphocytes (PBL). As expected, no TCR signals were detected from non-IP lung tissue controls.
Results:
The cases demonstrated substantial CD3+ T cell lung infiltrates. The usage of repertoires of TCR Va/Vb in the lung differed from those in PBL, with certain TCR V gene families detected more frequently in lung tissue, suggesting a pivotal role for T cells in the pathogenesis of IP associated with PM. This is the first robust demonstration of selective TCR repertoire usage and its differential expression in lung tissue versus PBL.
Conclusion:
These findings strongly suggest a pathogenic contribution of organ-specific oligoclonal T cell accumulation through antigen-driven immune mechanisms, implying potential development of immunospecific treatments such as molecular-targeted therapies.
Acknowledgements
The authors thank G. Deshpande, MD, for help with editing.
This study was supported by the Ministry of Education, Science and Technology in Japan.
Keywords:
Interstitial Lung Disease,
Interstitial pneumonia,
Polymyositis,
Dermatomyositis,
Lung biopsy,
Cell infiltrates,
phenotypes,
T cell,
T cell receptor (TCR),
T cell receptor repertoir,
PCR,
hybridization assay,
Humans
Conference:
15th International Congress of Immunology (ICI), Milan, Italy, 22 Aug - 27 Aug, 2013.
Presentation Type:
Abstract
Topic:
Immune-mediated disease pathogenesis
Citation:
Takeda
A,
Fukushima
Y,
Matsutani
T,
Haji
Y,
Rokutanda
R,
Suyama
Y,
Kishimoto
M,
Yamaguchi
K and
Okada
M
(2013). Implication of antigen-driven mechanisms in the pathogenesis of interstitial pneumonia associated with polymyositis.
Front. Immunol.
Conference Abstract:
15th International Congress of Immunology (ICI).
doi: 10.3389/conf.fimmu.2013.02.00414
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Received:
11 Apr 2013;
Published Online:
22 Aug 2013.
*
Correspondence:
Dr. Akira Takeda, International University of Health and Welfare Hospital, Division of Clinical Immunology & Rheumatology, Nasushiobara, Tochigi, 329-2763, Japan, atakeda123@gmail.com