Dr. Jennifer Lund

A Role for Regulatory T cells in Anti-viral Immunity

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. Additionally, recent work has highlighted the importance and role of these regulatory cells during immunity to infectious disease, a time during which it is important to generate a robust immune response such that the infectious agent can be cleared from the body, allowing for recovery from illness. Thus, the question arises as to how Tregs can participate in both of these goals so important to human survival - preventing damaging immune responses to self while at the same time allowing for the generation of immune responses in order to fight off foreign infectious agents.

We recently identified a novel and unexpected role for Tregs in the protective immune response to infection. Specifically, in examining the early response to herpes simplex-2 (HSV-2) infection, we found that Tregs can assist in the coordination of a timely trafficking of immune effector cells to the infected tissues, where they can then perform their respective jobs in fighting off infection. However, we also found that Tregs suppress immunity early after infection, as we observed decreased levels of interferons in the LNs when Tregs were present as compared to Treg-ablated mice. This latter finding is in line with work done previously by others to show that Tregs at other stages of various microbial infections can function to limit the late adaptive immune response, thereby minimizing associated tissue damage while at the same time preventing or diminishing pathogen clearance. These seemingly opposing roles may be dependent on the location (infection site vs. lymphoid tissues), timing (innate, adaptive, or memory immune response), and mode of action during the course of infection, and therefore we hypothesize that the specific and unique role of regulatory T cells during virus infections can vary with each of these factors. Thus, my research program will examine these issues, focusing on mucosal viral infections, as this is the route via which the general population encounters the majority of common viruses of major public health importance. Specifically, we are interested in addressing the role of Tregs during the immune response to primary and secondary challenge with genital HSV-2 infection, as this has important implications for vaccine design for sexually transmitted infections. Secondly, we would like to determine if Tregs must be antigen-specific in order to respond to genital HSV-2 infection, similarly to classical effector T cells. Finally, we will extend our studies of the role of Tregs during infection to a second common mucosal infection that is considered to be a major public health threat, influenza virus infection. We expect that results from these studies will help to reveal the roles of Tregs during various types of mucosal viral infections that infect different mucosal surfaces of the body, as well as the different roles that Tregs could play at various phases of the immune response to viruses. We expect that knowledge gained from this research program will assist in the generation of improved clinical interventions for mucosal viral infections such as vaccines, as we must understand how to best model vaccines in order to allow Tregs to effectively assist in the protective immune responses to viruses.