title: Loss of naive T cells and repertoire constriction predict poor response to vaccination in old primates.
abstract: Aging is usually accompanied by diminished immune protection upon infection or vaccination. Although aging results in well-characterized changes in the T cell compartment of long-lived, outbred, and pathogen-exposed organisms, their relevance for primary Ag responses remain unclear. Therefore, it remains unclear whether and to what extent the loss of naive T cells, their partial replacement by oligoclonal memory populations, and the consequent constriction of TCR repertoire limit the Ag responses in aging primates. We show in this study that aging rhesus monkeys (Macaca mulatta) exhibit poor CD8 T cell and B cell responses in the blood and poor CD8 responses in the lungs upon vaccination with the modified vaccinia strain Ankara. The function of APCs appeared to be maintained in aging monkeys, suggesting that the poor response was likely intrinsic to lymphocytes. We found that the loss of naive CD4 and CD8 T cells, and the appearance of persisting T cell clonal expansions predicted poor CD8 responses in individual monkeys. There was strong correlation between early CD8 responses in the transitory CD28+ CD62L- CD8+ T cell compartment and the peak Ab titers upon boost in individual animals, as well as a correlation of both parameters of immune response to the frequency of naive CD8+ T cells in old but not in adult monkeys. Therefore, our results argue that T cell repertoire constriction and naive cell loss have prognostic value for global immune function in aging primates.
authors.affiliation: Vaccine and Gene Therapy Institute, Oregon National Primate Research Center, Oregon Health and Science University, Beaverton, OR 97006, USA.
authors.forename: Luka
authors.initials: L
authors.lastname: Cicin-Sain
authors.forename: Susan
authors.initials: S
authors.lastname: Smyk-Pearson
authors.forename: Sue
authors.initials: S
authors.lastname: Smyk-Paerson
authors.forename: Noreen
authors.initials: N
authors.lastname: Currier
authors.forename: Laura
authors.initials: L
authors.lastname: Byrd
authors.forename: Caroline
authors.initials: C
authors.lastname: Koudelka
authors.forename: Tammie
authors.initials: T
authors.lastname: Robinson
authors.forename: Gwendolyn
authors.initials: G
authors.lastname: Swarbrick
authors.forename: Shane
authors.initials: S
authors.lastname: Tackitt
authors.forename: Alfred
authors.initials: A
authors.lastname: Legasse
authors.forename: Miranda
authors.initials: M
authors.lastname: Fischer
authors.forename: Dragana
authors.initials: D
authors.lastname: Nikolich-Zugich
authors.forename: Byung
authors.initials: B
authors.lastname: Park
authors.forename: Theodore
authors.initials: T
authors.lastname: Hobbs
authors.forename: Cynthia J
authors.initials: CJ
authors.lastname: Doane
authors.forename: Motomi
authors.initials: M
authors.lastname: Mori
authors.forename: Michael K
authors.initials: MK
authors.lastname: Axthelm
authors.forename: Michael T
authors.initials: MT
authors.lastname: Axthelm
authors.forename: Deborah A
authors.initials: DA
authors.lastname: Lewinsohn
authors.forename: Janko
authors.initials: J
authors.lastname: Nikolich-Zugich
mesh_terms: D000375:Aging / Q000276:immunology*; D000818:Animals; D017951:Antigen Presentation / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002469:Cell Separation; D003713:Dendritic Cells / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D008213:Lymphocyte Activation / Q000276:immunology; D008253:Macaca mulatta; D008297:Male; D013601:T-Lymphocytes / Q000276:immunology*; D014611:Vaccination