Mass Cytometry Identifies Distinct Lung CD4+ T Cell Patterns in Löfgren’s Syndrome and Non-Löfgren’s Syndrome Sarcoidosis

Frontiers in Immunology

Tadepally Lakshmikanth¹  Jaromir Mikes¹  Yang Chen¹  Adnane Achour¹  Petter Brodin²  Anders Eklund³  Ylva Kaiser³  Johan Grunewald³ 

[1] Department of Infectious Diseases, Karolinska University Hospital, Stockholm, Sweden;Department of Neonatology, Karolinska University Hospital, Stockholm, Sweden;Respiratory Medicine Unit, Department of Medicine, Solna and Center for Molecular Medicine, Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden;Science for Life Laboratory, Department of Medicine, Karolinska Institutet, Stockholm, Sweden;

关键词: sarcoidosis;    mass cytometry;    bronchoalveolar lavage;    CD4+ T cells;    Löfgren’s syndrome;    granuloma;   

DOI  :  10.3389/fimmu.2017.01130

来源: DOAJ

【 摘 要 】

Sarcoidosis is a granulomatous disorder of unknown etiology, characterized by accumulation of activated CD4+ T cells in the lungs. Disease phenotypes Löfgren’s syndrome (LS) and “non-LS” differ in terms of clinical manifestations, genetic background, HLA association, and prognosis, but the underlying inflammatory mechanisms largely remain unknown. Bronchoalveolar lavage fluid cells from four HLA-DRB1*03+ LS and four HLA-DRB1*03− non-LS patients were analyzed by mass cytometry, using a panel of 33 unique markers. Differentially regulated CD4+ T cell populations were identified using the Citrus algorithm, and t-stochastic neighborhood embedding was applied for dimensionality reduction and single-cell data visualization. We identified 19 individual CD4+ T cell clusters differing significantly in abundance between LS and non-LS patients. Seven clusters more frequent in LS patients were characterized by significantly higher expression of regulatory receptors CTLA-4, PD-1, and ICOS, along with low expression of adhesion marker CD44. In contrast, 12 clusters primarily found in non-LS displayed elevated expression of activation and effector markers HLA-DR, CD127, CD39, as well as CD44. Hierarchical clustering further indicated functional heterogeneity and diverse origins of T cell receptor Vα2.3/Vβ22-restricted cells in LS. Finally, a near-complete overlap of CD8 and Ki-67 expression suggested larger influence of CD8+ T cell activity on sarcoid inflammation than previously appreciated. In this study, we provide detailed characterization of pulmonary T cells and immunological parameters that define separate disease pathways in LS and non-LS. With direct association to clinical parameters, such as granuloma persistence, resolution, or chronic inflammation, these results provide a valuable foundation for further exploration and potential clinical application.

【 授权许可】

Unknown