Thymus-resident memory CD8+ T cells mediate local immunity

Eur J Immunol. 2013 Sep;43(9):2295-304. doi: 10.1002/eji.201343519. Epub 2013 Jun 26.

Abstract

The thymus is a primary lymphoid organ responsible for production and selection of T cells. Nonetheless, mature T cells and in particular activated T cells can reenter the thymus. Here, we identified memory CD8(+) T cells specific for lymphocytic choriomeningitis virus or vaccinia virus in the thymus of mice long-time after the infection. CD8(+) T cells were mainly located in the thymic medulla, but also in the cortical areas. Interestingly, virus-specific memory CD8(+) T cells in the thymus expressed the cell surface markers CD69 and CD103 that are characteristic of tissue-resident memory T cells in a time-dependent manner. Kinetic analyses and selective depletion of peripheral CD8(+) T cells by antibodies further revealed that thymic virus-specific memory CD8(+) T cells did not belong to the circulating pool of lymphocytes. Finally, we demonstrate that these thymus-resident virus-specific memory CD8(+) T cells efficiently mounted a secondary proliferative response, exhibited immediate effector functions and were able to protect the thymus from lymphocytic choriomeningitis virus reinfection. In conclusion, the present study not only describes for the first time virus-specific memory CD8(+) T cells with characteristics of tissue-resident memory T (T(RM)) cells in a primary lymphoid organ but also extends our knowledge about local T-cell immunity in the thymus.

Keywords: CD103; CD69; E-cadherin; Tissue-resident memory T (TRM) cells; Viral infections.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adoptive Transfer
  • Animals
  • Antigens, CD / biosynthesis
  • Antigens, Differentiation, T-Lymphocyte / biosynthesis
  • CD8-Positive T-Lymphocytes / immunology*
  • Cells, Cultured
  • Immunologic Memory*
  • Integrin alpha Chains / biosynthesis
  • Lectins, C-Type / biosynthesis
  • Lymphocyte Activation
  • Lymphocyte Count
  • Lymphocytic Choriomeningitis / immunology
  • Lymphocytic Choriomeningitis / prevention & control
  • Lymphocytic choriomeningitis virus / immunology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Secondary Prevention
  • T-Lymphocytes, Cytotoxic / immunology
  • Thymus Gland / immunology*
  • Vaccinia virus / immunology*

Substances

  • Antigens, CD
  • Antigens, Differentiation, T-Lymphocyte
  • CD69 antigen
  • Integrin alpha Chains
  • Lectins, C-Type
  • alpha E integrins