Memory CD8 T-cell compartment grows in size with immunological experience

Nature. 2009 Jan 8;457(7226):196-9. doi: 10.1038/nature07486. Epub 2008 Nov 12.

Abstract

Memory CD8 T cells, generated by natural pathogen exposure or intentional vaccination, protect the host against specific viral infections. It has long been proposed that the number of memory CD8 T cells in the host is inflexible, and that individual cells are constantly competing for limited space. Consequently, vaccines that introduce over-abundant quantities of memory CD8 T cells specific for an agent of interest could have catastrophic consequences for the host by displacing memory CD8 T cells specific for all previous infections. To test this paradigm, we developed a vaccination regimen in mice that introduced as many new long-lived memory CD8 T cells specific for a single vaccine antigen as there were memory CD8 T cells in the host before vaccination. Here we show that, in contrast to expectations, the size of the memory CD8 T-cell compartment doubled to accommodate these new cells, a change due solely to the addition of effector memory CD8 T cells. This increase did not affect the number of CD4 T cells, B cells or naive CD8 T cells, and pre-existing memory CD8 T cells specific for a previously encountered infection were largely preserved. Thus, the number of effector memory CD8 T cells in the mammalian host adapts according to immunological experience. Developing vaccines that abundantly introduce new memory CD8 T cells should not necessarily ablate pre-existing immunity to other infections.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • B-Lymphocytes / cytology
  • CD4-Positive T-Lymphocytes / cytology
  • CD8-Positive T-Lymphocytes / cytology*
  • CD8-Positive T-Lymphocytes / immunology*
  • Cells, Cultured
  • Hyaluronan Receptors / metabolism
  • Immunodominant Epitopes / immunology
  • Immunologic Memory / immunology*
  • L-Selectin / metabolism
  • Lymphocyte Count*
  • Lymphocytic choriomeningitis virus / immunology
  • Mice
  • Mice, Inbred C57BL
  • Vaccination
  • Viral Vaccines / administration & dosage
  • Viral Vaccines / immunology

Substances

  • Cd44 protein, mouse
  • Hyaluronan Receptors
  • Immunodominant Epitopes
  • Viral Vaccines
  • L-Selectin