Emerging patterns of regulatory T cell function in tuberculosis

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.