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Human IL-6RhiTIGIT- CD4+CD127lowCD25+ T cells display potent in vitro suppressive capacity and a distinct Th17 profile.
Ferreira, Ricardo C; Rainbow, Daniel B; Rubio García, Arcadio; Pekalski, Marcin L; Porter, Linsey; Oliveira, João J; Waldron-Lynch, Frank; Wicker, Linda S; Todd, John A.
Affiliation
  • Ferreira RC; JDRF/Wellcome Trust Diabetes and Inflammation Laboratory, Wellcome Trust Centre for Human Genetics, Nuffield Department of Medicine, NIHR Oxford Biomedical Research Centre, University of Oxford, Oxford, UK; JDRF/Wellcome Trust Diabetes and Inflammation Laboratory, Department of Medical Genetics, NIH
  • Rainbow DB; JDRF/Wellcome Trust Diabetes and Inflammation Laboratory, Wellcome Trust Centre for Human Genetics, Nuffield Department of Medicine, NIHR Oxford Biomedical Research Centre, University of Oxford, Oxford, UK; JDRF/Wellcome Trust Diabetes and Inflammation Laboratory, Department of Medical Genetics, NIH
  • Rubio García A; JDRF/Wellcome Trust Diabetes and Inflammation Laboratory, Wellcome Trust Centre for Human Genetics, Nuffield Department of Medicine, NIHR Oxford Biomedical Research Centre, University of Oxford, Oxford, UK; JDRF/Wellcome Trust Diabetes and Inflammation Laboratory, Department of Medical Genetics, NIH
  • Pekalski ML; JDRF/Wellcome Trust Diabetes and Inflammation Laboratory, Wellcome Trust Centre for Human Genetics, Nuffield Department of Medicine, NIHR Oxford Biomedical Research Centre, University of Oxford, Oxford, UK; JDRF/Wellcome Trust Diabetes and Inflammation Laboratory, Department of Medical Genetics, NIH
  • Porter L; JDRF/Wellcome Trust Diabetes and Inflammation Laboratory, Department of Medical Genetics, NIHR Cambridge Biomedical Research Centre, Cambridge Institute for Medical Research, University of Cambridge, Cambridge, UK.
  • Oliveira JJ; JDRF/Wellcome Trust Diabetes and Inflammation Laboratory, Department of Medical Genetics, NIHR Cambridge Biomedical Research Centre, Cambridge Institute for Medical Research, University of Cambridge, Cambridge, UK.
  • Waldron-Lynch F; Experimental Medicine and Immunotherapeutics, Department of Medicine, NIHR Cambridge Biomedical Research Centre, University of Cambridge, Cambridge, UK; NIHR Cambridge Clinical Trial Unit, Cambridge NHS University Hospitals Trust, Cambridge Biomedical Research Centre, University of Cambridge, Cambri
  • Wicker LS; JDRF/Wellcome Trust Diabetes and Inflammation Laboratory, Wellcome Trust Centre for Human Genetics, Nuffield Department of Medicine, NIHR Oxford Biomedical Research Centre, University of Oxford, Oxford, UK; JDRF/Wellcome Trust Diabetes and Inflammation Laboratory, Department of Medical Genetics, NIH
  • Todd JA; JDRF/Wellcome Trust Diabetes and Inflammation Laboratory, Wellcome Trust Centre for Human Genetics, Nuffield Department of Medicine, NIHR Oxford Biomedical Research Centre, University of Oxford, Oxford, UK; JDRF/Wellcome Trust Diabetes and Inflammation Laboratory, Department of Medical Genetics, NIH
Clin Immunol ; 179: 25-39, 2017 06.
Article in En | MEDLINE | ID: mdl-28284938
ABSTRACT
To date many clinical studies aim to increase the number and/or fitness of CD4+CD127lowCD25+ regulatory T cells (Tregs) in vivo to harness their regulatory potential in the context of treating autoimmune disease. Here, we sought to define the phenotype and function of Tregs expressing the highest levels of IL-6 receptor (IL-6R). We have identified a population of CD4+CD127lowCD25+ TIGIT- T cells distinguished by their elevated IL-6R expression that lacked expression of HELIOS, showed higher CTLA-4 expression, and displayed increased suppressive capacity compared to IL-6RhiTIGIT+ Tregs. IL-6RhiTIGIT- CD127lowCD25+ T cells contained a majority of cells demethylated at FOXP3 and displayed a Th17 transcriptional signature, including RORC (RORγt) and the capacity of producing both pro- and anti-inflammatory cytokines, such as IL-17, IL-22 and IL-10. We propose that in vivo, in the presence of IL-6-associated inflammation, the suppressive function of CD4+CD127lowCD25+ FOXP3+IL-6RhiTIGIT- T cells is temporarily disarmed allowing further activation of the effector functions and potential pathogenic tissue damage.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: CD4-Positive T-Lymphocytes / T-Lymphocyte Subsets Type of study: Prognostic_studies Limits: Adolescent / Adult / Humans / Male / Middle aged Language: En Journal: Clin Immunol Journal subject: ALERGIA E IMUNOLOGIA Year: 2017 Document type: Article
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: CD4-Positive T-Lymphocytes / T-Lymphocyte Subsets Type of study: Prognostic_studies Limits: Adolescent / Adult / Humans / Male / Middle aged Language: En Journal: Clin Immunol Journal subject: ALERGIA E IMUNOLOGIA Year: 2017 Document type: Article