The effect of regulatory T cells on an age-altered specific CD8 T cell response following influenza infection

Abstract

The elderly population is a major user of our health care resources. With this population of people growing faster than any other age group, it is important to find ways to reduce the increasingly high morbidity and mortality rates due to infections.Several studies have demonstrated that both aged mice and humans have a reduced CD8 T cell response to influenza infection. Further, it has been demonstrated that these alterations result from both intrinsic and extrinsic factors. Recently, it has been observed that there is an increase in the regulatory T cells (Treg cell) percentage in aged mice. No study has evaluated if this increase in Treg cells could be an extrinsic factor which suppresses the expansion and function of CD8 T cell responses during acute influenza infection. Therefore, we hypothesized that a major contributor to the extrinsic changes that effect T cell responses in aged mice are Treg cells.We compared the phenotype and function of Treg cells from aged and young mice. Interestingly in vitro depletion of Treg cells had no effect on CD8 T cell responses in young or aged mice. Further there appears to be no significant differences in the ability of Treg cells from aged mice to suppress specific CD8 T cells isolated from TCR transgenic (Tg) mice compared to Treg cells isolated from young mice.Although we found no differences in the function of Treg cells of aged compared to young mice in vitro, this does not mean that Treg cells do not demonstrate an age-associated differential impact in vivo following influenza infection. To evaluate the potential impact of Treg cells of aged mice on CD8 T cell expansion and function we studied the kinetics of Treg cells following influenza infection of young and aged mice. Following influenza infection Treg cells expand in aged but not young mice. Further the peak of CD8 T cell expansion and IFN-γ production in aged mice coincides with contraction of expanded Treg cell percentage and activation. We believe that this increased expansion early during infection in aged mice interferes with CD8 T cell expansion and function.%%%%Ph.D., Immunology – Drexel University, 2010