Enumeration of T Cells Specific for RD1‐Encoded Antigens Suggests a High Prevalence of LatentMycobacterium tuberculosisInfection in Healthy Urban Indians

Abstract

Knowledge of the prevalence of latent Mycobacterium tuberculosis infection is crucial for effective tuberculosis control, but tuberculin skin test surveys have major limitations, including poor specificity because of the broad 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-Guérin (BCG) and most environmental mycobacteria. We recently identified circulating ESAT-6-specific T cells as an accurate marker of M. tuberculosis infection. Here, interferon-gamma-secreting T cells specific for peptides derived from ESAT-6 and a second RD1 gene product, CFP10, were enumerated in 100 prospectively recruited healthy adults in Bombay (Mumbai), India. Eighty percent responded to >/=1 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 latent M. tuberculosis infection in urban India.

Interferon Gamma Response to Combinations 38 kDa/CFP‐10, 38 kDa/MPT‐64, ESAT‐6/MPT‐64 and ESAT‐6/CFP‐10, Each Related to a Single Recombinant Protein of Mycobacterium tuberculosis in Individuals from Tuberculosis Endemic Areas

“…Our results with these two individual antigens were 66% and 47%, respectively, and corroborate previous studies with ESAT-6 in Brazil (4). In contrast to the African studies, India and Europe response to CFP-10 is higher than ESAT-6; there may thus be a relationship between patients' geographic diversity and immune response (3,5,22). Interestingly, we found that the rate of TST Ϫ responders to ESAT-6 was low (17%, meanϭ78.24Ϯ 28.95 pg/ml), contrary to the data from Gambia, India (30% and 80%, respectively), and from a previous investigation in Brazil (80%) (4,23,32).…”

Evaluation of T-Cell Responses to Novel RD1- and RD2-EncodedMycobacterium tuberculosisGene Products for Specific Detection of Human Tuberculosis Infection

“…Control participants were healthy, BCG-vaccinated laboratory personnel from regions with a low prevalence of TB and with no known exposure to M. tuberculosis. All had recently tested negative by IFN-␥ ELISPOT assay with 35 overlapping 15-mer peptides spanning the lengths of ESAT-6 and CFP10, as previously described (24). Epidemiological data regarding place of birth, any period of residence in higherprevalence regions, and absence of TB contact were collected from these volunteers at the point of venipuncture.…”

“…Studies using several different assays, including lymphoproliferation, gamma interferon (IFN-␥) enzyme-linked immunosorbent assay (ELISA), and IFN-␥ enzyme-linked immunospot (ELISPOT) assay, have shown that they are strong targets of the cellular immune response in animal models, TB patients, and contacts (4,11,24,28,30,35,(37)(38)(39). However, we know very little about the remaining seven RD1 gene products.…”

Nuevas herramientas para la detección de la tuberculosis latente.

“…El ELISPOT fue positivo en 80% de los casos en Bombay, India, y 0% en el Reino Unido, incluso en 33 que habían sido previamente vacunados con BCG. La tuberculina detectó 98% y 85% de infección latente en estas dos poblaciones, respectivamente (39). La sobreestimación del PPD puede deberse a los falsos positivos que presenta esta prueba en personas vacunadas con BCG, o expuestas a micobacterias ambientales.…”