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Cytomegalovirus Exposure in the Elderly Does Not Reduce CD8 T Cell Repertoire Diversity

Paul Lindau1,2, Rithun Mukherjee3, Miriam V Gutschow2

  • 1Molecular and Cellular Biology Graduate Program, University of Washington School of Medicine, Seattle, WA 98195; plindau@uw.edu hrobins@fredhutch.org.

Journal of Immunology (Baltimore, Md. : 1950)
|December 14, 2018
PubMed

Insights

Aging and Cytomegalovirus (CMV) infection impair immune function. This study found that while CMV expands T cell clones in older adults, it does not reduce overall T cell diversity, suggesting functional changes, not repertoire loss, cause diminished immunity.

Area of Science:

  • Immunology
  • Gerontology
  • Infectious Diseases

Background:

  • Immune system effectiveness declines with age, increasing infection susceptibility.
  • Chronic Cytomegalovirus (CMV) infection exacerbates immune dysfunction and mortality in the elderly.
  • CMV infection causes large CD8+ T cell expansions, potentially reducing T cell repertoire diversity and impairing responses to new infections.

Purpose of the Study:

  • To investigate the impact of CMV infection on the structure and diversity of the human T cell repertoire in aging individuals.
  • To test the hypothesis that T cell repertoire contraction occurs due to CMV-driven clonal expansions.

Main Methods:

  • Utilized TCR β-chain immunosequencing to analyze peripheral blood T cell repertoires.
  • Quantified the proportion of the T cell repertoire occupied by the most frequent clones.
  • Compared T cell repertoire structure and diversity between CMV seropositive and seronegative individuals across different age groups.

Main Results:

  • The proportion of the T cell repertoire occupied by the top 0.1% of clones is larger in CMV seropositive individuals and increases with age.
  • The elderly T cell repertoire expands to accommodate CMV-driven clonal expansions.
  • The underlying T cell repertoire diversity and clonal structure are preserved despite large CMV-reactive T cell clones.

Conclusions:

  • Maintenance of large CMV-reactive T cell clones does not necessarily compromise the overall T cell repertoire diversity in the elderly.
  • Diminished immunity in elderly individuals with CMV may stem from alterations in T cell function rather than a reduction in CD8+ T cell repertoire diversity.

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