Skip to main content
eScholarship
Open Access Publications from the University of California

Divergent phenotypes of human regulatory T cells expressing the receptors TIGIT and CD226

  • Author(s): Fuhrman, CA
  • Yeh, WI
  • Seay, HR
  • Lakshmi, PS
  • Chopra, G
  • Zhang, L
  • Perry, DJ
  • McClymont, SA
  • Yadav, M
  • Lopez, MC
  • Baker, HV
  • Zhang, Y
  • Li, Y
  • Whitley, M
  • Von Schack, D
  • Atkinson, MA
  • Bluestone, JA
  • Brusko, TM
  • et al.
Abstract

© 2015 by The American Association of Immunologists, Inc. Regulatory T cells (Tregs) play a central role in counteracting inflammation and autoimmunity. A more complete understanding of cellular heterogeneity and the potential for lineage plasticity in human Treg subsets may identify markers of disease pathogenesis and facilitate the development of optimized cellular therapeutics. To better elucidate human Treg subsets, we conducted direct transcriptional profiling of CD4+FOXP3+Helios+ thymic-derived Tregs and CD4+FOXP3+Helios- T cells, followed by comparison with CD4+FOXP3-Helios- T conventional cells. These analyses revealed that the coinhibitory receptor T cell Ig and ITIM domain (TIGIT) was highly expressed on thymic-derived Tregs. TIGIT and the costimulatory factor CD226 bind the common ligand CD155. Thus, we analyzed the cellular distribution and suppressive activity of isolated subsets of CD4+CD25+CD127lo/- T cells expressing CD226 and/or TIGIT. We observed TIGIT is highly expressed and upregulated on Tregs after activation and in vitro expansion, and is associated with lineage stability and suppressive capacity. Conversely, the CD226+TIGIT- population was associated with reduced Treg purity and suppressive capacity after expansion, along with a marked increase in IL-10 and effector cytokine production. These studies provide additional markers to delineate functionally distinct Treg subsets that may help direct cellular therapies and provide important phenotypic markers for assessing the role of Tregs in health and disease.

Many UC-authored scholarly publications are freely available on this site because of the UC Academic Senate's Open Access Policy. Let us know how this access is important for you.

Main Content
Current View