Regulatory T cells shape the effector and memory T cell response to virus infection in the tissues (170.15)

Abstract

Abstract Regulatory T cells (Tregs) are well known for their role in dampening the immune responses to self-antigens and thereby helping to prevent autoimmune disease. However, they must also permit immune responses to occur against foreign infectious agents. Using a mouse model of West Nile Virus (WNV) infection, we examined Treg kinetics, trafficking, and activation at both acute and memory time points. We showed that Treg numbers increase in both the secondary lymphoid organs and CNS after infection, and become activated similar to effector T cells. Using the Foxp3DTR knock-in mice, we have performed experiments to study the course of WNV infection in the presence or absence of Tregs. We found that compared to ”normal” mice, Treg deficient mice had increased antigen-driven production of IFN-g from both CD4 and CD8 T cells in both the spleen and CNS. Additionally, Treg deficient mice had an increased frequency of poly-functional T cells. In mice lacking Tregs, there were greater numbers of short lived effector CD8+ cells at acute infection time points in both the spleen and brain. At a memory time point, there were significantly fewer antigen-specific T cells present in the CNS of mice deficient in Tregs at the time of infection compared to Treg sufficient mice. Studies are currently underway to examine the role of Tregs in CD4 memory using this Treg depletion model.