Regulatory T cells with reduced repressor capacities are extensively amplified in pulmonary sarcoid lesions and sustain granuloma formation

• Published in: Clinical immunology (Orlando, Fla.) Fla.), 2011-07, Vol.140 (1), p.71-83
• Main Authors: Rappl, Gunter, Pabst, Stefan, Riemann, Dagmar, Schmidt, Annette, Wickenhauser, Claudia, Schütte, Wolfgang, Hombach, Andreas A, Seliger, Barbara, Grohé, Christian, Abken, Hinrich
• Format: Article
• Language: English
• Subjects: Adult; Aged; Allergy and Immunology; Biological and medical sciences; CD7; Cell Proliferation; Cell Separation; Chronic inflammation; Female; Flow Cytometry; Fluorescent Antibody Technique; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Granuloma - immunology; Humans; Immunohistochemistry; Immunologic Memory - immunology; Immunosenescence; Male; Medical sciences; Middle Aged; Sarcoidosis; Sarcoidosis, Pulmonary - immunology; Sarcoidosis. Granulomatous diseases of unproved etiology. Connective tissue diseases. Elastic tissue diseases. Vasculitis; T-Lymphocyte Subsets - immunology; T-Lymphocytes, Regulatory - immunology; Treg cells; Young Adult
• ISSN: 1521-6616; 1521-7035
• DOI: 10.1016/j.clim.2011.03.015

Abstract Sarcoidosis can evolve into a chronic disease with persistent granulomas accompanied by progressive fibrosis. While an unlimited inflammatory response suggests an impaired immune control in sarcoid lesions, it stands in contrast to the massive infiltration with CD4+ CD25high FoxP3+ regulatory T cells. We here revealed that those Treg cells in affected lung lesions were mainly derived from activated natural Treg cells with GARP (LRRC32)-positive phenotype but exhibited reduced repressor capacities despite high IL-10 and TGF-beta 1 levels. The repressive capacity of blood Treg cells, in contrast, was not impaired compared to age-matched healthy donors. Treg derived cells in granuloma lesions have undergone extensive rounds of amplifications indicated by shortened telomeres compared to blood Treg cells of the same patient. Lesional Treg derived cells moreover secreted pro-inflammatory cytokines including IL-4 which sustains granuloma formation through fibroblast amplification and the activation of mast cells, the latter indicated by the expression of membrane-bound oncostatin M.