T Regulatory Cells and BCG as a Vaccine against Tuberculosis: An Overview

Bacille Calmette Guerin (BCG), which has been used since 1921 as the only vaccine against tuberculosis (TB), protects poorly, if at all, against pulmonary tuberculosis among adults in high incident developing countries. This failure has been attributed to the possible down modulating action of T regulatory cells (Tregs), which can be stimulated by environmental mycobacteria and expanded by BCG vaccination. Tregs induced at the site of BCG vaccination may interfere with protection against tuberculosis. This communication describes the contribution of Tregs towards dampening the efficacy of BCG and plausible approaches to countering this down modulating effect of Tregs. Probably, antigen specific inhibition of the local recruitment of Tregs whilst avoiding generalised disturbance of immune homeostasis could prove to be worthwhile. Alternatively, drugs with short half life may achieve more acceptable transient inhibition of Tregs function than the prolonged action of monoclonal antibodies. Evolving novel safe strategies is a challenge for developing a better anti TB vaccine.