title: A population biological approach to understanding the maintenance and loss of the T-cell repertoire during aging.
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.
authors.affiliation: Biology, Emory University, Atlanta, GA.
authors.forename: Philip L F
authors.initials: PL
authors.lastname: Johnson
authors.forename: Jörg J
authors.initials: JJ
authors.lastname: Goronzy
authors.forename: Rustom
authors.initials: R
authors.lastname: Antia
mesh_terms: D000375:Aging / Q000276:immunology*; D006801:Humans; D018655:Lymphocyte Count; D018448:Models, Immunological; D013601:T-Lymphocytes / Q000166:cytology* / Q000276:immunology* / Q000821:virology
keywords: T-cell receptors; memory; repertoire evolution