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

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 IFN gamma. Likewise, old horses have increased frequency of CD8(-)IFN gamma(+) T cells and TNF alpha producing cells. We also show that old horses have elevated levels of IL-1 beta, IL-15, IL-18 and TNF alpha gene expression in peripheral blood and significant levels of TNF alpha protein in serum, all characteristics of inflamm-aging. (C) 2008 Elsevier Ireland Ltd. All rights reserved.