Unidirectional development of CD8+ central memory T cells into protective Listeria-specific effector memory T cells

Katharina M. Huster, Martina Koffler, Christian Stemberger, Matthias Schiemann, Hermann Wagner, Dirk H. Busch

Research output: Contribution to journalArticlepeer-review

74 Scopus citations

Abstract

Three distinct subsets of antigen-experienced CD8+ T cells have been identified so far: short-living effector T cells (TEC) and two long-living subsets, described as central (TCM) and effector memory (TEM) T cells. The lineage relationships of these subpopulations as well as their involvement in protection have not yet been conclusively determined. We recently described a novel marker combination (CD127 and CD62L) to identify all three major CD8+ T cell subsets in mice infected with Listeria monocytogenes (L.m.). Extensive lineage relationship analyses on highly purified subpopulations after in vitro and in vivo stimulation demonstrated that TCM can develop into TEM or TEC, whereas TEM can only progress to TEC cells. Short-living TEC never regained a TEM or TCM phenotype. Thesea data strongly suggest a hierarchical and unidirectional order of developmental stages. In vivo priming protocols that preferentially induced one of the different CD8+ T cell subsets demonstrated that predominance of TEM (CD40 stimulation) correlated best with effective protection against L.m., whereas generation of neither TCM (by immunization with heat-killed L.m.) nor TEC (by systemic co-administration of CpG during primary infection) conferred substantial long-term protective immunity. These findings have important implications for the design of more effective T cell-based vaccines.

Original languageEnglish
Pages (from-to)1453-1464
Number of pages12
JournalEuropean Journal of Immunology
Volume36
Issue number6
DOIs
StatePublished - Jun 2006

Keywords

  • CD8 T cells
  • Intracellular bacteria
  • Protective immunity
  • T cell memory

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