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A population biological approach to understanding the maintenance and loss of the T‐cell repertoire during aging
Author(s) -
Johnson Philip L. F.,
Goronzy Jörg J.,
Antia Rustom
Publication year - 2014
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1111/imm.12244
Subject(s) - repertoire , biology , immune system , population , epigenetics , immunology , acquired immune system , evolutionary biology , neuroscience , genetics , demography , sociology , physics , gene , acoustics
Summary 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.