RELATIONSHIP BETWEEN CD8+ T CELL IMMUNITY AND AGING USING WEST NILE VIRUS INFECTION AS A MODEL

Abstract

<p>The incidence and severity of infectious diseases increases in elderly people (>60 years of age). It is believe that the age-associated changes in the immune system, termed immunosenescence, lead to diminished effectiveness of the immune system leaving the aged susceptible to infectious pathogens and associated diseases. The limited efficacy of the currently available vaccines in elderly populations contribute immensely to the frequency of infectious diseases in the globally growing aging population. As such, the demographic shift warrants the development of effective prophylactic vaccines for the elderly.</p> <p>West Nile virus (WNV) became endemic in North America in 1999, and although it infects people of all ages, the incidence of severe neuroinvasive disease is more prevalent in the elderly. I hypothesized that the susceptibility of the elderly towards severe WNV disease is a consequence of aberrant immune function, and specifically lack of functional virus-specific CD8+ T cells. Contrary to my hypothesis, I found that the magnitude, breadth and functionality of WNV-specific CD8+ T cells were not different between the age cohorts. These results argue that advanced age does not limit the development of functional CD8+ T cell responses following primary infections with an acute virus. Furthermore, the aged members of our cohort maintained functional CD8+ T cells to cytomegalovirus (CMV) and Epstein-Barr virus (EBV), common persistent viruses.</p> <p>Collectively, my results demonstrate that development of vaccines designed to elicit CD8+ T cell immunity may be warranted for elderly individuals and perhaps live vectors should be considered for this population.</p>