Immunosenescence and inflamm-aging in the horse.

摘要

Age-associated changes in immune function can be described as bidirectional in terms of there being diminished or immunosenescent characteristics and enhanced or inflamm-aging characteristics. Decreased T cell proliferation is a hallmark characteristic of immunosenescence and contributes to reduced responsiveness to vaccination and infectious agents, in particular influenza. Inflamm-aging is characterized by increased production of inflammatory cytokines which have been associated with increased morbidity and mortality in the elderly. Age-related obesity is thought to play a role in inflamm-aging. Improving our understanding of the aged immune system has become an urgent issue due to the increasing geriatric population of humans and horses. The overall hypothesis of this research was that changes in immune function of the old horse (≥ 20 years) involve both, immunosenescent and inflamm-aging (in vitro & in vivo) characteristics, and decreased immunity to equine influenza vaccination and infection. Mechanisms of T cell replicative senescence were investigated and results demonstrate that decreased proliferation is due to an accumulation of non-dividing T cells that are not susceptible to increased apoptosis but remain capable of producing significant amounts of cytokines. Inflamm-aging was characterized both in vitro and in vivo. Results indicate that old horses have increased pro-inflammatory cytokine production lymphocytes and monocytes, and they have increased pro-inflammatory cytokine gene expression and protein production in circulation. The effect of body condition, body weight and adiposity on inflamm-aging responses in old horses was determined. Decreasing adiposity in old horses reduced age-associated increases of inflammatory cytokines both in vitro and in vivo; demonstrating that age-related obesity potentially plays a role in the dysregulation of inflammatory cytokine production by old horses. Lastly, the immunological and physiological response of aged horses to a live recombinant-vectored equine influenza virus (EIV) vaccine and subsequent challenge infection was evaluated. Results confirm that vaccination stimulates significant EIV-specific antibody responses in old horses, but impaired CMI responses. Nevertheless, the vaccine provided protection against clinical disease and virus shedding in old horses. Overall, this body of work provides novel information characterizing age-related changes in immune function of the old horse.;Keyword: Aging, Immunosenescence, Inflamm-aging, Vaccination, Horse