title: Nonrandom attrition of the naive CD8+ T-cell pool with aging governed by T-cell receptor:pMHC interactions.
abstract: Immunity against new infections declines in the last quartile of life, as do numbers of naive T cells. Peripheral maintenance of naive T cells over the lifespan is necessary because their production drastically declines by puberty, a result of thymic involution. We report that this maintenance is not random in advanced aging. As numbers and diversity of naive CD8(+) T cells declined with aging, surviving cells underwent faster rates of homeostatic proliferation, were selected for high T-cell receptor:pMHC avidity, and preferentially acquired "memory-like" phenotype. These high-avidity precursors preferentially responded to infection and exhibited strong antimicrobial function. Thus, T-cell receptor avidity for self-pMHC provides a proofreading mechanism to maintain some of the fittest T cells in the otherwise crumbling naive repertoire, providing a degree of compensation for numerical and diversity defects in old T cells.
authors.affiliation: Department of Immunobiology and the Arizona Center on Aging, University of Arizona College of Medicine, Tucson, AZ 85724, USA.
authors.forename: Brian D
authors.initials: BD
authors.lastname: Rudd
authors.forename: Vanessa
authors.initials: V
authors.lastname: Venturi
authors.forename: Gang
authors.initials: G
authors.lastname: Li
authors.forename: Partha
authors.initials: P
authors.lastname: Samadder
authors.forename: James M
authors.initials: JM
authors.lastname: Ertelt
authors.forename: Sing Sing
authors.initials: SS
authors.lastname: Way
authors.forename: Miles P
authors.initials: MP
authors.lastname: Davenport
authors.forename: Janko
authors.initials: J
authors.lastname: Nikolich-Žugich
mesh_terms: D000375:Aging / Q000276:immunology*; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology* / Q000276:immunology; D049109:Cell Proliferation; D016922:Cellular Senescence / Q000276:immunology; D006680:HLA Antigens / Q000276:immunology*; D006706:Homeostasis / Q000276:immunology; D007109:Immunity / Q000276:immunology; D007156:Immunologic Memory; D018655:Lymphocyte Count; D051379:Mice; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*
chemical_list: D006680:HLA Antigens; D011948:Receptors, Antigen, T-Cell