The role of natural regulatory T cells in infection.

Naturally occurring regulatory T cells (T(Reg)) suppress multiple cell types of the immune system to maintain dominant tolerance to protect from autoimmunity, down-modulate anti-tumor immunity and restrain allergic diseases. In addition to these functions, T(Reg) can alter effector responses to invading pathogens, leading to a variety of outcomes affecting both the host and infecting microorganisms. Here, we review how T(Reg) can influence the immune responses to chronic infections where pathogen-specific T(Reg) can contribute to pathogen persistence and, in some cases, concomitant immunity, as well as control immunopathology associated with robust immune responses. We also review the data on T(Reg) during acute infection, focusing on the questions these studies raise regarding the most appropriate model(s) to examine T(Reg) during infection. Finally, we discuss the ways in which the T(Reg) function can be altered by invading pathogens and how these can be exploited to develop methods therapeutically to influence disease and vaccine outcomes.