Regulatory T cells characterized by low Id3 expression are highly suppressive and accumulate during chronic infection

// Katharina S. Rauch 1, 2 , Miriam Hils 1, 2 , Alexandra J. Menner 1, 2 , Mikael Sigvardsson 3 , Susana Minguet 1, 2, 4 , Peter Aichele 1, 5 , Christian Schachtrup 6 and Kristina Schachtrup 1, 2 1 Center for Chronic Immunodeficiency (CCI), Medical Center – University of Freiburg, Faculty of Medicine, Freiburg, Germany 2 Faculty of Biology, Freiburg, Germany 3 Institution for Clinical and Experimental Sciences, Faculty of Health Sciences, Linkoping University, Linkoping, Sweden 4 Centre for Biological Signalling Studies BIOSS, University of Freiburg, Germany and Max Planck Institute of Immunology and Epigenetics, Freiburg, Germany 5 Institute for Immunology, Medical Center, University of Freiburg, Faculty of Medicine, Freiburg, Germany 6 Institute of Anatomy and Cell Biology, Faculty of Medicine, Freiburg, Germany Correspondence to: Kristina Schachtrup, email: kristina.schachtrup@uniklinik-freiburg.de Keywords: Treg cells; chronic infection; transcription; Id proteins; immunology Received: September 26, 2017      Accepted: October 10, 2017      Published: October 27, 2017 ABSTRACT Foxp3 + regulatory T (Treg) cells are broadly divided into naive-like and activated Treg cells, however recent studies suggest further Treg cell heterogeneity. Treg cells contribute to impaired T cell responses in chronic infections, but the role of specific Treg cell subpopulations in viral infections is not well defined. Here, we report that activated Treg cells are separated into two transcriptionally distinct subpopulations characterized by low or high expression of the transcriptional regulator Id3 . Id3 lo Treg cells are a highly suppressive Treg cell subpopulation, expressing elevated levels of immunomodulatory molecules and are capable of broadly targeting T cell responses. Viral infection and interleukin-2 promote the differentiation of Id3 hi into Id3 lo Treg cells and during chronic infection Id3 lo Treg cells are the predominant Treg cell population. Thus, our report provides a framework, in which different activated Treg cell subpopulations specifically affect immune responses, possibly contributing to T cell dysfunction in chronic infections.