Tentative T cells: memory cells are quick to respond, but slow to divide

PLoS Pathog. 2008 Apr 11;4(4):e1000041. doi: 10.1371/journal.ppat.1000041.

Abstract

T cell memory is a cornerstone of protective immunity, and is the key element in successful vaccination. Upon encountering the relevant pathogen, memory T cells are thought to initiate cell division much more rapidly than their naïve counterparts, and this is thought to confer a significant biological advantage upon an immune host. Here, we use traceable TCR-transgenic T cells to evaluate this proposed characteristic in CD4+ and CD8+ memory T cells. We find that, even in the presence of abundant antigen that was sufficient to induce in vivo IFNgamma production by memory T cells, both memory and naïve T cells show an extended, and indistinguishable, delay in the onset of proliferation. Although memory cells can detect, and respond to, virus infection within a few hours, their proliferation did not begin until approximately 3 days after infection, and occurred simultaneously in all anatomical compartments. Thereafter, cell division was extraordinarily rapid for both naïve and memory cells, with the latter showing a somewhat accelerated accumulation. We propose that, by permitting memory T cells to rapidly exert their effector functions while delaying the onset of their proliferation, evolution has provided a safeguard that balances the risk of infection against the consequences of severe T cell-mediated immunopathology.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adoptive Transfer
  • Animals
  • Brefeldin A / pharmacology
  • CD4-Positive T-Lymphocytes / cytology*
  • CD4-Positive T-Lymphocytes / drug effects
  • CD4-Positive T-Lymphocytes / metabolism
  • CD8-Positive T-Lymphocytes / cytology*
  • CD8-Positive T-Lymphocytes / drug effects
  • CD8-Positive T-Lymphocytes / metabolism
  • Cell Division
  • Cell Proliferation
  • Disease Models, Animal
  • Immune Tolerance
  • Immunologic Memory*
  • Interferon-gamma / metabolism
  • Lymph Nodes / cytology
  • Lymph Nodes / drug effects
  • Lymph Nodes / immunology
  • Lymphocyte Activation
  • Lymphocytic Choriomeningitis / immunology
  • Lymphocytic Choriomeningitis / virology
  • Lymphocytic choriomeningitis virus / immunology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic / immunology
  • Protein Synthesis Inhibitors / pharmacology
  • Receptors, Antigen, T-Cell / metabolism
  • Spleen / cytology
  • Spleen / drug effects
  • Spleen / immunology

Substances

  • Protein Synthesis Inhibitors
  • Receptors, Antigen, T-Cell
  • Brefeldin A
  • Interferon-gamma