A Coronin 1-Dependent Decision Switch in Juvenile Mice Determines the Population of the Peripheral Naive T Cell Compartment

J Immunol. 2017 Oct 1;199(7):2421-2431. doi: 10.4049/jimmunol.1700438. Epub 2017 Aug 18.

Abstract

Following thymic maturation, T cells egress as recent thymic emigrants to peripheral lymphoid organs where they undergo an additional maturation step to mature naive T cells that circulate through secondary lymphoid organs ready to be activated upon pathogenic challenges. Thymic maturation and peripheral T cell survival depend on several signaling cascades, but whether a dedicated mechanism exists that exclusively regulates homeostasis of mature naive T cells without affecting thymocytes and/or recent thymic emigrants remains unknown. In this article, we provide evidence for a specific and exclusive role of the WD repeat containing protein coronin 1 in the maintenance of naive T cells in peripheral lymphoid organs. We show that coronin 1 is dispensable for thymocyte survival and development, egress from the thymus, and survival of recent thymic emigrants. Importantly, coronin 1-deficient mice possessed comparable levels of peripheral T cells within the first 2 wk after birth but failed to populate the peripheral T cell compartment at later stages. Furthermore, dendritic cell- and IL-2/7-dependent T cell survival was found to be independent of coronin 1. Together, these results suggest the existence of a hitherto unrecognized coronin 1-dependent decision switch early during life that is responsible for peripheral naive T cell survival and homeostasis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD4-Positive T-Lymphocytes / physiology
  • Cell Survival*
  • Dendritic Cells / metabolism
  • Homeostasis
  • Interleukin-2 / pharmacology
  • Interleukin-7 / pharmacology
  • Mice
  • Mice, Inbred C57BL
  • Microfilament Proteins / deficiency
  • Microfilament Proteins / genetics
  • Microfilament Proteins / metabolism*
  • Signal Transduction
  • T-Lymphocyte Subsets / metabolism
  • T-Lymphocyte Subsets / physiology*
  • Thymocytes / drug effects
  • Thymocytes / physiology
  • Thymus Gland / anatomy & histology
  • Thymus Gland / cytology*
  • Thymus Gland / immunology

Substances

  • Interleukin-2
  • Interleukin-7
  • Microfilament Proteins
  • coronin proteins