Loss of naive T cells and repertoire constriction predict poor response to vaccination in old primates

Luka Čičin-Šain, Sue Smyk-Paerson, Noreen Currier, Laura Byrd, Caroline Koudelka, Tammie Robinson, Gwendolyn Swarbrick, Shane Tackitt, Alfred Legasse, Miranda Fischer, Dragana Nikolich-Žugich, Byung Park, Theodore Hobbs, Cynthia J. Doane, Motomi Mori, Michael T. Axthelm, Deborah A. Lewinsohn, Janko Nikolich-Žugich

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82 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)6739-6745
Number of pages7
JournalJournal of Immunology
Volume184
Issue number12
DOIs
StatePublished - Jun 15 2010

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ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Čičin-Šain, L., Smyk-Paerson, S., Currier, N., Byrd, L., Koudelka, C., Robinson, T., Swarbrick, G., Tackitt, S., Legasse, A., Fischer, M., Nikolich-Žugich, D., Park, B., Hobbs, T., Doane, C. J., Mori, M., Axthelm, M. T., Lewinsohn, D. A., & Nikolich-Žugich, J. (2010). Loss of naive T cells and repertoire constriction predict poor response to vaccination in old primates. Journal of Immunology, 184(12), 6739-6745. https://doi.org/10.4049/jimmunol.0904193