Viral inoculum dose impacts memory T-cell inflation

Eur J Immunol. 2014 Apr;44(4):1046-57. doi: 10.1002/eji.201343946. Epub 2014 Mar 7.


Memory T-cell inflation develops during certain persistent viral infections and is characterized by the accumulation and maintenance of large numbers of effector-memory T cells, albeit with varying degrees in size and phenotype among infected hosts. The underlying mechanisms that control memory T-cell inflation are not yet fully understood. Here, we dissected CMV-specific memory T-cell formation and its connection to the initial infectious dose by varying the inoculum size. After low dose inoculum with mouse CMV, the accumulation of inflationary memory T cells was severely hampered and correlated with reduced reservoirs of latent virus in nonhematopoietic cells and diminished antigen-driven T-cell proliferation. Moreover, lowering of the initial viral dose turned the characteristic effector memory-like inflationary T cells into more central memory-like cells as evidenced by the cell-surface phenotype of CD27(high) , CD62L(+) , CD127(+) , and KLRG1(-) , and by improved secondary expansion potential. These data show the impact of the viral inoculum on the degree of memory T-cell inflation and provide a rationale for the observed variation of human CMV-specific T-cell responses in terms of magnitude and phenotype.

Keywords: CD8+ T cells; CMV; Memory T-cell inflation; T-cell activation; Viral immunity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD8-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / metabolism
  • CD8-Positive T-Lymphocytes / virology
  • Cell Proliferation
  • Cells, Cultured
  • Flow Cytometry
  • Herpesviridae Infections / immunology*
  • Herpesviridae Infections / virology
  • Host-Pathogen Interactions / immunology
  • Humans
  • Immunologic Memory / immunology*
  • Immunophenotyping
  • Interleukin-7 Receptor alpha Subunit / immunology
  • Interleukin-7 Receptor alpha Subunit / metabolism
  • L-Selectin / immunology
  • L-Selectin / metabolism
  • Lectins, C-Type
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Muromegalovirus / immunology*
  • Muromegalovirus / physiology
  • Receptors, Immunologic / immunology
  • Receptors, Immunologic / metabolism
  • Tumor Necrosis Factor Receptor Superfamily, Member 7 / immunology
  • Tumor Necrosis Factor Receptor Superfamily, Member 7 / metabolism
  • Virus Latency / immunology


  • Interleukin-7 Receptor alpha Subunit
  • Klrg1 protein, mouse
  • Lectins, C-Type
  • Receptors, Immunologic
  • Tumor Necrosis Factor Receptor Superfamily, Member 7
  • L-Selectin