Dramatic increase in naïve T cell turnover is linked to loss of naïve T cells from old primates

Luka Čičin-Šain, Ilhem Messaoudi, Byung Park, Noreen Currier, Shannon Planer, Miranda Fischer, Shane Tackitt, Dragana Nikolich-Žugich, Alfred Legasse, Michael K. Axthelm, Louis J. Picker, Motomi Mori, Janko Nikolich-Žugich

Research output: Contribution to journalArticle

96 Scopus citations

Abstract

The loss of naïve T cells is a hallmark of immune aging. Although thymic involution is a primary driver of this naïve T cell loss, less is known about the contribution of other mechanisms to the depletion of naïve T cells in aging primates. We examined the role of homeostatic cycling and proliferative expansion in different T cell subsets of aging rhesus macaques (RM). BrdU incorporation and the expression of the G1-M marker Ki-67 were elevated in peripheral naïve CD4 and even more markedly in the naïve CD8 T cells of old, but not young adult, RM. Proliferating na?̈ve cells did not accumulate in old animals. Rather, the relative size of the naïve CD8 T cell compartment correlated inversely to its proliferation rate. Likewise, T cell receptor diversity decreased in individuals with elevated naïve CD8 T cell proliferation. This apparent contradiction was explained by a significant increase in turnover concomitant with the naïve pool loss. The turnover increased exponentially when the naïve CD8 T cell pool decreased below 4% of total blood CD8 cells. These results link the shrinking naïve T cell pool with a dramatic increase in homeostatic turnover, which has the potential to exacerbate the progressive exhaustion of the naïve pool and constrict the T cell repertoire. Thus, homeostatic T cell proliferation exhibits temporal antagonistic pleiotropy, being beneficial to T cell maintenance in adulthood but detrimental to the long-term T cell maintenance in aging individuals.

Original languageEnglish (US)
Pages (from-to)19960-19965
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume104
Issue number50
DOIs
StatePublished - Dec 11 2007
Externally publishedYes

Keywords

  • Aging
  • CD8
  • Homeostasis

ASJC Scopus subject areas

  • General

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    Čičin-Šain, L., Messaoudi, I., Park, B., Currier, N., Planer, S., Fischer, M., Tackitt, S., Nikolich-Žugich, D., Legasse, A., Axthelm, M. K., Picker, L. J., Mori, M., & Nikolich-Žugich, J. (2007). Dramatic increase in naïve T cell turnover is linked to loss of naïve T cells from old primates. Proceedings of the National Academy of Sciences of the United States of America, 104(50), 19960-19965. https://doi.org/10.1073/pnas.0705905104