1. High-Dimensional T Helper Cell Profiling Reveals a Broad Diversity of Stably Committed Effector States Uncovers Interlineage Relationships
- Author
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Lea Pohlmeier, Luigi Tortola, Bernd Bodenmiller, Andrea Jacobs, Franziska Ampenberger, Manfred Kopf, Franz-Josef Obermair, University of Zurich, Tortola, Luigi, and Kopf, Manfred
- Subjects
0301 basic medicine ,medicine.medical_treatment ,Immunology ,Cell ,610 Medicine & health ,Biology ,Lymphocyte Activation ,Mice ,03 medical and health sciences ,Th2 Cells ,0302 clinical medicine ,Antigen ,Immunity ,medicine ,Animals ,Humans ,Immunology and Allergy ,Mass cytometry ,Transcription factor ,Cells, Cultured ,Mice, Knockout ,2403 Immunology ,Effector ,Pyroglyphidae ,Cell Differentiation ,T helper cell ,2725 Infectious Diseases ,Th1 Cells ,Asthma ,Cell biology ,Mice, Inbred C57BL ,030104 developmental biology ,Infectious Diseases ,Cytokine ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,2723 Immunology and Allergy ,Cytokines ,Th17 Cells ,11493 Department of Quantitative Biomedicine - Abstract
CD4+ T helper (Th) cells are fundamental players in immunity. Based on the expression of signature cytokines and transcription factors, several Th subsets have been defined. Th cells are thought to be far more heterogeneous and multifunctional than originally believed, but characterization of the full diversity has been hindered by technical limitations. Here, we employ mass cytometry to analyze the diversity of Th cell responses generated in vitro and in animal disease models, revealing a vast heterogeneity of effector states with distinct cytokine footprints. The diversities of cytokine responses established during primary antigen encounters in Th1- and Th2-cell-polarizing conditions are largely maintained after secondary challenge, regardless of the new inflammatory environment, highlighting many of the identified states as stable Th cell sublineages. We also find that Th17 cells tend to upregulate Th2-cell-associated cytokines upon challenge, indicating a closer developmental connection between Th17 and Th2 cells than previously anticipated. © 2020 Elsevier Inc.
- Published
- 2020
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