Tr1 cells and the counter-regulation of immunity: Natural mechanisms and therapeutic applications

Maria Grazia Roncarolo, Silvia Gregori, Rosa Bacchetta, Manuela Battaglia

Research output: Chapter in Book/Report/Conference proceedingChapter

Abstract

T regulatory Type 1 (Tr1) cells are adaptive T regulatory cells characterized by the ability to secrete high levels of IL-10 and minimal amounts of IL-4 and IL-17. Recently, CD49b and LAG-3 have been identified as Tr1-cell-specific biomarkers in mice and humans. Tr1 cells suppress T-cell- and antigen-presenting cell- (APC) responses primarily via the secretion of IL-10 and TGF-β. In addition, Tr1 cells release granzyme B and perforin and kill myeloid cells. Tr1 cells inhibit T cell responses also via cell-contact dependent mechanisms mediated by CTLA-4 or PD-1, and by disrupting the metabolic state of T effector cells via the production of the ectoenzymes CD39 and CD73. Tr1 cells were first described in peripheral blood of patients who developed tolerance after HLA-mismatched fetal liver hematopoietic stem cell transplant. Since their discovery, Tr1 cells have been proven to be important in maintaining immunological homeostasis and preventing T-cell-mediated diseases. Furthermore, the possibility to generate and expand Tr1 cells in vitro has led to their utilization as cellular therapy in humans. In this chapter we summarize the unique and distinctive biological properties of Tr1 cells, the well-known and newly discovered Tr1-cell biomarkers, and the different methods to induce Tr1 cells in vitro and in vivo. We also address the role of Tr1 cells in infectious diseases, autoimmunity, and transplant rejection in different pre-clinical disease models and in patients. Finally, we highlight the pathological settings in which Tr1 cells can be beneficial to prevent or to cure the disease.

Original languageEnglish
Title of host publicationCurrent Topics in Microbiology and Immunology
Pages39-68
Number of pages30
Volume380
DOIs
Publication statusPublished - 2014

Publication series

NameCurrent Topics in Microbiology and Immunology
Volume380
ISSN (Print)0070217X
ISSN (Electronic)21969965

ASJC Scopus subject areas

  • Immunology and Allergy
  • Microbiology (medical)
  • Immunology
  • Microbiology

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    Roncarolo, M. G., Gregori, S., Bacchetta, R., & Battaglia, M. (2014). Tr1 cells and the counter-regulation of immunity: Natural mechanisms and therapeutic applications. In Current Topics in Microbiology and Immunology (Vol. 380, pp. 39-68). (Current Topics in Microbiology and Immunology; Vol. 380). https://doi.org/10.1007/978-3-662-43492-5-3