Homeostatic properties and phenotypic maturation of murine CD4+ pre-thymic emigrants in the thymus

PLoS One. 2013;8(2):e56378. doi: 10.1371/journal.pone.0056378. Epub 2013 Feb 11.

Abstract

After a tightly regulated developmental program in the thymus, "mature" single positive (SP) thymocytes leave the thymus and enter the periphery. These newly arrived recent thymic emigrants (RTEs) are phenotypically and functionally immature, and will complete a dynamic maturation in the peripheral lymphoid organs before being licensed to be resident naïve T cells. To study the early events occurring in the RTE maturation process, we identified the phenotype of CD4(+) pre-RTEs, a population of CD4(+) SP thymocytes that have acquired the thymus egress capability. Compared to peripheral naïve T cells, CD4(+) pre-RTEs displayed superior survival capability in lymphoreplete mice and faster proliferation under lymphopenic condition. The differences in Bcl2/Bim expression and/or heightened IL-7 signaling pathway may account for the pre-RTEs' better responsiveness to homeostatic signals. Qa2, the expression of which indicates the phenotypic maturation of SPs and RTEs, was found to be upregulated in CD4(+) pre-RTEs in thymic perivascular space. Migratory dendritic cells that surround this region contribute to Qa2 expression in pre-RTEs. The dendritic cell-driven Qa2 induction of CD4(+) pre-RTEs is independent of MHC class II and Aire molecules.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, CD / metabolism
  • Antigens, Differentiation, T-Lymphocyte / metabolism
  • CD4-Positive T-Lymphocytes / cytology*
  • CD4-Positive T-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / metabolism
  • Cell Proliferation
  • Cell Survival
  • Dendritic Cells / cytology
  • Dendritic Cells / immunology
  • Homeostasis / immunology*
  • Lectins, C-Type / metabolism
  • Lymphocyte Activation
  • Mice
  • Mice, Inbred C57BL
  • Phenotype*
  • Signal Transduction / immunology
  • Thymocytes / cytology
  • Thymocytes / immunology
  • Thymus Gland / immunology*
  • Up-Regulation

Substances

  • Antigens, CD
  • Antigens, Differentiation, T-Lymphocyte
  • CD69 antigen
  • Lectins, C-Type

Grants and funding

This work was supported by grants from the Natural Basic Research Program of China (2010CB945301, QG, 2011CB711000, QG, and 2011CB946100, YZ), the National Natural Sciences Foundation of China (31070787, QG, 30830091, YZ), Program for New Century Excellent Talents in University (NCET-10-0175/BMU20100005), and the Research Fund for the Doctoral Program of Higher Education (20100001110049). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.