Human CD4 and CD8 regulatory T cells in infectious diseases and vaccination.

Regulatory T cells (Tregs) are crucial players in balancing inflammation and antigen specific immune responses. In chronic infectious diseases, Tregs dampen inflammation to limit tissue damage, but they can also inhibit ensuing effector immunity, thereby impairing pathogen clearance. Chronic persistent infections by human pathogens such as parasites, viruses, and (myco)bacteria can all result in the induction of both CD4(+) and CD8(+) Tregs. However, among the many different subsets of Tregs that are induced, mostly CD4(+) Tregs have been studied. A remarkably increased frequency has been observed at the site of infection, supporting a role in pathogen containment. Indeed, antigen specificity has been demonstrated for several pathogen derived antigens. Here we review different classes of human Tregs in infectious diseases, including CD4 and CD8 Treg subsets. A better understanding of the induction and activity of Tregs is relevant for the design of better vaccines that optimally induce effector immunity without co-induction of excessive Treg activity.