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

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• 作者：Gunter Rappl^a ; ^h ; ¹ ; ^{gunter.rappl@uni-koeln.de"" rel=""nofollow} ; Stefan Pabst^b ; ¹ ; Dagmar Riemann^c ; Annette Schmidt^d ; Claudia Wickenhauser^e ; Wolfgang Schü ; tte^f ; Andreas A. Hombach^a ; Barbara Seliger^c ; Christian Grohé ; ^g ; Hinrich Abken^a ; ^h
• 关键词：Sarcoidosis ; Treg cells ; Chronic inflammation ; Immunosenescence ; CD7
• 刊名：Clinical Immunology
• 出版年：2011
• 出版时间：July 2011
• 年：2011
• 卷：140
• 期：1
• 页码：71-83
• 全文大小：1440 K

文摘

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⁺CD25^highFoxP3⁺ 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.