T cell responses to mycobacterial catalase-peroxidase profile a pathogenic antigen in systemic sarcoidosis

Edward S. Chen, Jan Wahlström, Zhimin Song, Matthew H. Willett, Maria Wikén, Rex C. Yung, Erin E. West, John F. McDyer, Ying Zhang, Anders Eklund, Johan Grunewald, David R. Moller

Research output: Contribution to journalArticlepeer-review

Abstract

Sarcoidosis is a systemic granulomatous disease associated with local epithelioid granulomas, CD4+T cells, and Th1 cytokines. The tissue Ags that drive this granulomatous inflammation are uncertain. In this study, we used IFNγ-ELISPOT assays and flow cytometry to assess lung and blood T cell responses to the candidate pathogenic Ag, Mycobacterium tuberculosis catalase-peroxidase (mKatG) in patients with sarcoidosis from two centers. Despite differences in patient phenotypic, genetic, and prognostic characteristics, we report that T cell responses to mKatG were remarkably similar in these cohorts, with higher frequencies of mKatG-reactive, IFN-γ-expressing T cells in the blood of sarcoidosis patients compared with nontuberculosis sensitized healthy controls, and (in a subset) in greater numbers than T cells reactive to purified protein derivative. In sarcoidosis, mKatG-reactive CD4+Th1 cells preferentially accumulated in the lung, indicating a compartmentalized response. Patients with or without Löfgren syndrome had similar frequencies of mKatG specific IFN-γ-expressing blood T cells. Circulating mKatG-reactive T cells were found in chronic active sarcoidosis but not in patients with inactive disease. Together, these results demonstrate that T cell responses to mKatG in sarcoidosis fit a profile expected for a pathogenic Ag, supporting an immunotherapeutic approach to this disease.

Original languageEnglish (US)
Pages (from-to)8784-8796
Number of pages13
JournalJournal of Immunology
Volume181
Issue number12
DOIs
StatePublished - Dec 15 2008

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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