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Open Access Research

Immune correlates of aging in outdoor-housed captive rhesus macaques (Macaca mulatta)

Elizabeth S Didier12*, Chie Sugimoto3, Lisa C Bowers1, Imtiaz A Khan4 and Marcelo J Kuroda3

  • * Corresponding author: Elizabeth S Didier esdnda@tulane.edu

  • † Equal contributors

Author Affiliations

1 Division of Microbiology, Tulane National Primate Research Center, 18703 Three Rivers Road, Covington, LA, 70433, USA

2 Department of Tropical Medicine, School of Public Health and Tropical Medicine, Tulane University, New Orleans, New Orleans, LA, 70112, USA

3 Division of Immunology, Tulane National Primate Research Center, 18703 Three Rivers Road, Covington, LA, 70433, USA

4 Department of Microbiology, Immunology, and Tropical Medicine, Ross Hall Room 745, George Washington University, 2300 I Street, N.W, Washington D.C, 20037, USA

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Immunity & Ageing 2012, 9:25  doi:10.1186/1742-4933-9-25

Published: 14 November 2012

Abstract

Background

Questions remain about whether inflammation is a cause, consequence, or coincidence of aging. The purpose of this study was to define baseline immunological characteristics from blood to develop a model in rhesus macaques that could be used to address the relationship between inflammation and aging. Hematology, flow cytometry, clinical chemistry, and multiplex cytokine/chemokine analyses were performed on a group of 101 outdoor-housed captive rhesus macaques ranging from 2 to 24 years of age, approximately equivalent to 8 to 77 years of age in humans.

Results

These results extend earlier reports correlating changes in lymphocyte subpopulations and cytokines/chemokines with increasing age. There were significant declines in numbers of white blood cells (WBC) overall, as well as lymphocytes, monocytes, and polymorphonuclear cells with increasing age. Among lymphocytes, there were no significant declines in NK cells and T cells, whereas B cell numbers exhibited significant declines with age. Within the T cell populations, there were significant declines in numbers of CD4+ naïve T cells and CD8+ naïve T cells. Conversely, numbers of CD4+CD8+ effector memory and CD8+effector memory T cells increased with age. New multiplex analyses revealed that concentrations of a panel of ten circulating cytokines/chemokines, IFNγ, IL1b, IL6, IL12, IL15, TNFα, MCP1, MIP1α, IL1ra, and IL4, each significantly correlated with age and also exhibited concordant pairwise correlations with every other factor within this group. To also control for outlier values, mean rank values of each of these cytokine concentrations in relation to age of each animal and these also correlated with age.

Conclusions

A panel of ten cytokines/chemokines were identified that correlated with aging and also with each other. This will permit selection of animals exhibiting relatively higher and lower inflammation status as a model to test mechanisms of inflammation status in aging with susceptibility to infections and vaccine efficacy.

Keywords:
Inflammation; Inflamm-aging; Cytokine; Chemokine; Multiplex; Rhesus macaque; Aging; Animal model; Immune senescence; Blood