A population biological approach to understanding the maintenance and loss of the T-cell repertoire during aging

Philip L.F. Johnson, Jörg J. Goronzy, Rustom Antia

Research output: Contribution to journalReview articlepeer-review

23 Scopus citations

Abstract

The adaptive immune system requires a diverse T-cell repertoire to be able to respond to a wide variety of pathogens. Worryingly, the repertoire diversity declines dramatically in old age. As thymic output generates novel T cells, the conventional view holds that a decrease in this output with age is responsible for the loss in the repertoire. However, many additional factors affect the repertoire such as homeostatic turnover and antigen-dependent expansion in response to infection. Mathematical models taking a population biology perspective are important tools for understanding how the interplay between these factors affects the immune repertoire. These models suggest that thymic decline is not a major factor but rather that some combination of virus-induced proliferation and T-cell-intrinsic genetic or epigenetic changes gives rise to the oligoclonal expansions that cause the decline in T-cell diversity. We also discuss consequences for strategies to rejuvenate the immune repertoire in old age.

Original languageEnglish (US)
Pages (from-to)167-175
Number of pages9
JournalImmunology
Volume142
Issue number2
DOIs
StatePublished - Jun 2014

Keywords

  • Memory
  • Repertoire evolution
  • T-cell receptors

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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