Enumeration of T cells specific for RD1-encoded antigens suggests a high prevalence of latent Mycobacterium tuberculosis infection in healthy urban Indians

Knowledge of the prevalence of latent Mycobacterium tuberculosis infection is crucial for effective tuberculosis control, but tuberculin skin test sur veys have major limitations, including poor specificity because of the broa d antigenic cross-reactivity of tuberculin. The M. tuberculosis RD1 genomic segment encodes proteins, such as early secretory antigenic target (ESAT)- 6, that are absent from M. bovis bacille Calmette-Guerin (BCG) and most env ironmental mycobacteria. We recently identified circulating ESAT-6-specific T cells as an accurate marker of M. tuberculosis infection. Here, interfer on-gamma -secreting T cells specific for peptides derived from ESAT-6 and a second RD1 gene product, CFP10, were enumerated in 100 prospectively recru ited healthy adults in Bombay (Mumbai), India. Eighty percent responded to greater than or equal to1 antigen, and many donors had high frequencies of T cells that were specific for certain immunodominant peptides. In contrast , of 40 mostly BCG-vaccinated, United Kingdom-resident healthy adults, none responded to either antigen. This study suggests an 80% prevalence of late nt M. tuberculosis infection in urban India.