Long-lived memory CD8+ T cells are programmed by prolonged antigen exposure and low levels of cellular activation

Eur J Immunol. 2006 Apr;36(4):842-54. doi: 10.1002/eji.200535730.


CD8+ T cells play a crucial role in controlling intracellular pathogens. The level of memory CD8+ T cells developing after vaccination or infection influences the degree of T cell-mediated protection after secondary infection. We used defined animal models and infections/immunizations by replicating or non-replicating antigens to define on a molecular and cellular level in vivo the parameters that identify and shape long-lived CD8+ T cell memory. We show that the timing of antigen exposure during vaccination is key for the induction of long-lived T cell memory. Brief antigen exposure induced high numbers of effector cells but limited development of long-lived CD8+ memory T cells. In contrast, prolonged antigen exposure for up to 9 days induced similar numbers of effector T cells but additionally resulted in high levels of memory CD8+ T cells. Unexpectedly CD127 (IL-7Ralpha) expression on CD8+ T cells during the acute priming phase was a necessary but not sufficient requirement for entering the pool of long-lived antigen-independent memory CD8+ T cells. However, we provide strong evidence for the interpretation that programming of long-lived memory T cells was driven by low levels of transcription factor eomesodermin and protease inhibitor Spi2A as well as reduced phosphorylation of c-JUN.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens / immunology*
  • Antigens, Viral / immunology
  • CD8-Positive T-Lymphocytes / immunology*
  • Fluorescent Antibody Technique
  • Gene Expression / immunology
  • Immunologic Memory*
  • JNK Mitogen-Activated Protein Kinases / immunology
  • JNK Mitogen-Activated Protein Kinases / metabolism
  • Lymphocyte Activation / immunology*
  • Lymphocytic choriomeningitis virus / immunology
  • Mice
  • Mice, Inbred C57BL
  • Phosphorylation
  • Receptors, Interleukin-7 / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Serpins / immunology
  • Serpins / metabolism
  • T-Box Domain Proteins / immunology
  • T-Box Domain Proteins / metabolism
  • Vaccines / immunology*
  • Xenopus Proteins / immunology
  • Xenopus Proteins / metabolism


  • Antigens
  • Antigens, Viral
  • EOMES protein, Xenopus
  • Receptors, Interleukin-7
  • Serpina3k protein, mouse
  • Serpins
  • T-Box Domain Proteins
  • Vaccines
  • Xenopus Proteins
  • interleukin-7 receptor, alpha chain
  • JNK Mitogen-Activated Protein Kinases