Advanced age in horses affects divisional history of T cells and inflammatory cytokine production

• Published in: Mechanisms of ageing and development 2008-11, Vol.129 (11), p.656-664
• Main Authors: Adams, A.A., Breathnach, C.C., Katepalli, M.P., Kohler, K., Horohov, D.W.
• Format: Article
• Language: English
• Subjects: Age Factors; Aging; Aging - immunology; Animals; Apoptosis; Apoptosis - drug effects; Biological and medical sciences; Cell Proliferation - drug effects; Cells, Cultured; Cellular Senescence; Concanavalin A - pharmacology; Cytokines - genetics; Cytokines - metabolism; Development. Metamorphosis. Moult. Ageing; Fundamental and applied biological sciences. Psychology; Horses; Inflammation Mediators - metabolism; Inflammatory cytokines; Interferon-gamma - blood; Interleukins - blood; Mitogens - pharmacology; Models, Animal; Proliferation; RNA, Messenger - blood; T-Lymphocytes - drug effects; T-Lymphocytes - immunology; Tumor Necrosis Factor-alpha - blood; Vertebrates: anatomy and physiology, studies on body, several organs or systems
• ISSN: 0047-6374; 1872-6216
• DOI: 10.1016/j.mad.2008.09.004

A number of model systems have been employed to investigate age-associated changes in immune function. The purpose of the current study was to characterize senescent T cells and to investigate the inflamm-aging phenomenon both in vitro and in vivo using the old horse as a model. We examined whether decreased T cell proliferation induced by Con A is caused by increased apoptosis. We also utilized intracellular CFSE to analyze changes within each round of cell proliferation, in particular cytokine production. Intracellular staining with flow cytometry, RT-PCR, and ELISA were used to measure pro-inflammatory cytokines both in vitro and in vivo. While lymphocytes from old horses exhibit decreased proliferation, this is not the result of increased apoptosis. Instead, a larger percentage of the T cells remain in the parent generation and produce significant amounts of IFNγ. Likewise, old horses have increased frequency of CD8 −IFNγ + T cells and TNFα producing cells. We also show that old horses have elevated levels of IL-1β, IL-15, IL-18 and TNFα gene expression in peripheral blood and significant levels of TNFα protein in serum, all characteristics of inflamm-aging.