Fuel and brake of memory T cell inflation

Med Microbiol Immunol. 2019 Aug;208(3-4):329-338. doi: 10.1007/s00430-019-00587-9. Epub 2019 Mar 9.

Abstract

Memory T cell inflation is a process in which a large number of effector memory T cells accumulates in peripheral tissues. This phenomenon is observed upon certain low level persistent virus infections, but it is most commonly described upon infection with the β-herpesvirus Cytomegalovirus. Due to the induction of this large pool of functional effector CD8 T cells in peripheral tissues, the interest in using CMV-based vaccine vectors for vaccination purposes is rising. However, the exact mechanisms of memory T cell inflation are not yet fully understood. It is clear that repetitive exposure to antigen is a key determinant for memory inflation, and therefore the viral inoculum dose and the subsequent number of viral reactivation events strongly impact on the magnitude of the inflationary T cell pool. In addition, the number of CMV-specific CD8 T cells that is able to sense these reactivation events affects the size of the inflationary T cell pool. In the following, we will discuss factors that either promote or limit T cell inflation from both the virus and host perspective. These factors mostly operate by influencing the amount of available antigen or by affecting the T cell pool that is able to respond to the antigen. Furthermore, we will discuss the recent use of CMV-based vaccines in pre-clinical experimental settings, where these vectors have shown promising results by inducing prolonged effector memory T cell responses to foreign-introduced epitopes and thereby provided protection from subsequent virus or tumour challenges.

Keywords: CD8 T cell; Cytomegalovirus infection; Memory inflation.

Publication types

  • Review

MeSH terms

  • Antigens, Viral / immunology
  • CD8-Positive T-Lymphocytes / immunology*
  • Cytomegalovirus / growth & development
  • Cytomegalovirus / immunology*
  • Cytomegalovirus Infections / immunology*
  • Cytomegalovirus Infections / virology
  • Immunologic Memory*
  • Virus Activation
  • Virus Latency

Substances

  • Antigens, Viral