Background/Purpose:

The lung is frequently affected in connective tissue diseases (CTDs). Polymyositis (PM) is a major CTD characterized by idiopathic 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, which often have a poor prognosis and a high risk of mortality. 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.  Lung tissue was utilized in this study with the approval of the IRB.

Methods:

We had advantage of a rare opportunity to be able to precisely study the lung tissues which were obtained for the pathodiagnostic purpose by video-assisted thoracoscopy from the cases of earliest-stage IP associated with PM: one patient with IP of early usual IP (UIP) pattern and another patient with IP of nonspecific IP (NSIP) pattern. It lead us to immunohistochemically characterize the phenotype of lung-infiltrating lymphocytes from the lung biopsy specimens, and to analyze T-cell receptor α-chain (TCR Vα) and TCR β-chain (TCR Vβ) 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). We considered it important to perform TCR analysis from lung tissue in the earliest stage of IP because TCRs diversify with disease progression due to “determinant spreading” in which autoreactive T-cell responses, initiated by a single antigenic epitope, evolve into multiepitopic responses.     

Results:

The study with lung tissues of the initial stage of IP demonstrated substantial pulmonary CD3+ predominated T cell infiltrates. In both cases, patient A (early UIP pattern) and patient B (NSIP pattern), most of the mononuclear cells were CD3+ T-cells, accompanied by a subtle infiltration of B-cells (CD20+), and a minimal number of monocytes (CD19+). Of infiltrating T-cells, more CD4+ than CD8+ cells (in the ratio of four to one) were noted in both patients. The usage of repertoires of TCR Vα/Vβ 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.  As expected, no TCR signals were detected from non-IP lung tissue controls. 

Conclusion:

These findings clearly suggest a pathogenic contribution of organ-specific oligoclonal T cell accumulation through antigen-driven immune responses, implying potential elucidation of causative antigens as well as development of immuno-specific treatments such as molecular-targeted therapies.

ACR Meeting Abstracts - https://acrabstracts.org/abstract/t-cells-trigger-interstitial-pneumonia-in-polymyositis/