Abstract
Tuberculosis (TB) is one of the top 10 causes of mortality worldwide from a single infectious agent and has significant implications for global health. A major hurdle in the development of effective TB vaccines and therapies is the absence of defined immune-correlates of protection. In this context, the role of regulatory T cells (T(reg) ), which are essential for maintaining immune homeostasis, is even less understood. This review aims to address this knowledge gap by providing an overview of the emerging patterns of T(reg) function in TB. Increasing evidence from studies, both in animal models of infection and TB patients, points to the fact the role of T(regs) in TB is dependent on disease stage. While T(regs) might expand and delay the appearance of protective responses in the early stages of infection, their role in the chronic phase perhaps is to counter-regulate excessive inflammation. New data highlight that this important homeostatic role of T(regs) in the chronic phase of TB may be compromised by the expansion of activated human leucocyte antigen D-related (HLA-DR)(+) CD4(+) suppression-resistant effector T cells. This review provides a comprehensive and critical analysis of the key features of T(reg) cells in TB; highlights the importance of a balanced immune response as being important in TB and discusses the importance of probing not just T(reg) frequency but also qualitative aspects of T(reg) function as part of a comprehensive search for novel TB treatments.