NONHUMAN PRIMATE MODEL OF IMMUNOSENESCENCE AND VACCINATION

Tulane University Of Louisiana, New Orleans LA

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Abstract

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. The elderly population is growing in number and proportion to the total population. During aging, the immune system begins to falter, so methods to improve immune responses and vaccine efficacy in the elderly is a public health priority. Non-human primates are phylogenetically related and physiologically similar to humans and provide a useful model to study immunology of aging. The purpose of this study was to define changes in the peripheral immune system in rhesus macaques of varying ages. Flow cytometry of blood cells and multiplex cytokine levels in plasma were evaluated in 35 rhesus macaques ranging in age from 3.2 - 20 years. Linear regression was used to analyze the data for statistically significant changes (i.e. P 0.05) associated with age. Results indicated that with increasing age, significant declines were observed in numbers of neutrophils, eosinophils, basophils, and lymphocytes. No statistically significant changes in total numbers of monocytes, dendritic cells (DC), erythrocytes, or platelets were noted. Within the lymphocyte population, significant decreases in B lymphocytes were detected while numbers of total NK cells and T cells did not significantly change with increasing age. Examination within the T cell population, however, indicated significant declines in the number of naive CD4+ T cells and naive CD8+ T cells, as well as gd+ T cells with increasing age, whereas the number of CD8+ effector-memory T cells increased with age. Although the number of DCs did not significantly change with advancing age, the turnover rate of pDCs, as measured by BrdU-labeling and flow cytometry, was significantly higher in the 18-20 year-old group of animals compared to younger groups of animals. Among the cytokines tested in plasma using the Milliplex MAP non-human primate cytokine panel (23-mer) kit, TNF-a, IL-2, MCP-1, sCD40L, TGF-a, VEGF, and IL-18 levels significantly increased with increasing age of the animals whereas IL-5 was the only cytokine tested that decreased with increasing age. These early results provide a basis to further characterize immunosenescence in a non-human primate model, and for developing strategies to improve immune status and vaccine efficacy in the elderly.