Regulatory T cells in HIV infection: can immunotherapy regulate the regulator?

Regulatory T cells (Tregs) have a dominant role in self-tolerance and control of autoimmune diseases. These cells also play a pivotal role in chronic viral infections and cancer by limiting immune activation and specific immune response. The role of Tregs in HIV pathogenesis remains poorly understood as their function, changes according to the phases of infection. Tregs can suppress anti-HIV specific responses and conversely can have a beneficial role by reducing the deleterious impact of immune activation. We review the frequency, function and homing potential of Tregs in the blood and lymphoid tissues as well as their interaction with dendritic cells in the context of HIV infection. We also examine the new insights generated by recombinant IL-2 and IL-7 clinical trials in HIV-infected adults, including the immunomodulatory effects of Tregs. Based on their detrimental role in limiting anti-HIV responses, we propose Tregs as potential targets for immunotherapeutic strategies aimed at decreasing Tregs frequency and/or immunosuppressive function. However, such approaches require a better understanding of the time upon infection when interfering with Treg function may not cause a deleterious state of hyperimmune activation.