Regulatory T cells in virus infections

This review discusses situations when the magnitude and function of immune responses to virus infection are influenced by regulatory T cells (Tregs). The focus is on CD4(+)CD25(+) forkhead box protein 3(+) natural Tregs (nTregs). The immune response may be limited in magnitude and efficacy when animals with normal nTreg function are infected with virus. This limitation can be observed both in vitro and in vivo. In the case of herpes simplex virus (HSV), animals depleted of nTregs prior to infection more effectively control the virus. With some virus infections, Treg responses (either nTregs or interleukin-10-dependent adaptive Tregs) appear to contribute to immune dysfunction, accounting for viral persistence and chronic tissue damage. This may occur with hepatitis C virus and some retrovirus infections that include human immunodeficiency virus (HIV). Under other circumstances, the nTreg response is judged to be beneficial, as it may help limit the severity of tissue damage associated with an immunoinflammatory reaction to virus infection. Such a situation occurs in HSV-induced immunopathological lesions in the eye. With HIV, nTregs may help limit chronic immune activation that may precede collapse of the immune system. This review also discusses how virus infections become recognized by nTreg responses and how such responses might be manipulated to increase immunity or to limit virus-induced immunopathology.