Defective CD8 T cell responses in aged mice are due to quantitative and qualitative changes in virus-specific precursors

J Immunol. 2012 Feb 15;188(4):1933-41. doi: 10.4049/jimmunol.1101098. Epub 2012 Jan 13.

Abstract

Aging is associated with suboptimal CD8 T cell responses to viral infections. It is not clear whether these poor responses are due to environmental influences or quantitative and qualitative changes in the pool of responding CD8 T cells. Our studies demonstrated several deleterious age-related changes in the pool of Ag-specific CD8 T cells that respond to infection. The majority of CD8 T cells from uninfected aged mice was CD44(Hi) and had increased expression of inhibitory receptors including PD1, LAG3, 2B4, and CD160. These aged CD44(Hi) CD8 T cells were transcriptionally similar to exhausted CD8 T cells found during chronic infections. In addition, the number of virus-specific precursors in aged mice prior to infection was decreased up to 10-fold, and many of these Ag-specific precursors had high expression of CD44 and PD1. Finally, TCR transgenic studies demonstrated that the CD44(Hi) Ag-specific CD8 T cells from unimmunized aged and young mice were qualitatively inferior compared with CD44(Lo) CD8 T cells from aged or young donors. Thus, a decrease in precursor frequency as well as qualitative changes of CD8 T cells during aging are directly related to impaired immunity.

Publication types

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

MeSH terms

  • Aging / immunology*
  • Animals
  • Antigens, CD / biosynthesis
  • Arenaviridae Infections / immunology*
  • CD8-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / metabolism
  • Female
  • GPI-Linked Proteins / biosynthesis
  • Hyaluronan Receptors / analysis
  • Lymphocyte Activation Gene 3 Protein
  • Lymphocytic choriomeningitis virus / immunology
  • Lymphocytic choriomeningitis virus / metabolism
  • Lymphocytic choriomeningitis virus / pathogenicity
  • Mice
  • Programmed Cell Death 1 Receptor / biosynthesis
  • Receptors, Antigen, T-Cell / immunology*
  • Receptors, Antigen, T-Cell / metabolism
  • Receptors, Immunologic / biosynthesis
  • Signaling Lymphocytic Activation Molecule Family

Substances

  • Antigens, CD
  • Cd160 protein, mouse
  • Cd244a protein, mouse
  • GPI-Linked Proteins
  • Hyaluronan Receptors
  • Programmed Cell Death 1 Receptor
  • Receptors, Antigen, T-Cell
  • Receptors, Immunologic
  • Signaling Lymphocytic Activation Molecule Family
  • Lymphocyte Activation Gene 3 Protein