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

Vilma Decman1, Brian J Laidlaw, Travis A Doering

  • 1Department of Microbiology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA.

Insights

Aging impairs CD8 T cell immunity due to fewer virus-specific precursors and lower quality T cells. Aged CD8 T cells exhibit exhaustion markers, reducing immune response effectiveness against infections.

Area of Science:

  • Immunology
  • Aging Research
  • Infectious Disease

Background:

  • Aging is linked to diminished CD8 T cell responses during viral infections.
  • The causes of these suboptimal responses remain unclear, with possibilities including environmental factors or intrinsic changes in T cells.

Purpose of the Study:

  • To investigate age-related quantitative and qualitative changes in antigen-specific CD8 T cells.
  • To determine the impact of these changes on immune response to viral infections.

Main Methods:

  • Analysis of CD8 T cell populations in aged and young mice, focusing on CD44 expression and inhibitory receptors (PD1, LAG3, 2B4, CD160).
  • Transcriptional profiling of aged CD8 T cells.
  • Assessment of virus-specific precursor frequencies.
  • T cell receptor (TCR) transgenic studies to compare CD44(Hi) and CD44(Lo) CD8 T cell function.

Main Results:

  • Aged mice showed a majority of CD8 T cells with high CD44 expression and increased inhibitory receptors, resembling exhausted T cells.
  • Virus-specific CD8 T cell precursors decreased significantly (up to 10-fold) in aged mice, with many exhibiting high CD44 and PD1 expression.
  • CD44(Hi) CD8 T cells from aged mice were qualitatively inferior to CD44(Lo) cells, irrespective of donor age.

Conclusions:

  • Aging leads to a reduced number of virus-specific CD8 T cell precursors.
  • Qualitative defects in CD8 T cells, characterized by increased exhaustion markers and impaired function, contribute to decreased immunity in aged individuals.
  • Both decreased precursor frequency and altered T cell quality are directly implicated in impaired immune responses during aging.

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