Altered expression of antigen-specific memory and regulatory T cell subsets differentiate latent and active Tuberculosis.

Though one-third of the world population is infected with M. tuberculosis, only 5-10% of the infected individuals will develop active TB disease and rest will remain infected with no symptoms known as latent TB infection (LTBI). Identifying biomarkers that differentiate latent and active TB disease enables effective TB control, since early detection, treatment of active TB and preventive treatment of LTBI individuals are crucial steps involved in TB control. Here, we have evaluated the frequency of antigen specific memory and regulatory T cells (Tregs) in 15 healthy household contacts (HHC) and 15 pulmonary TB patients (PTB) to identify biomarkers for differential diagnosis of LTBI and active TB. Amongst all antigens tested in the present study, ESAT-6 specific CD4+ and CD8+ central memory cells (Tcm) showed 93% positivity in HHC and 20% positivity in PTB. The novel test antigens Rv0753c and Rv0009 both displayed 80% and 20% positivity in HHC and PTB respectively. In contrast to Tcm, effector memory T cells (Tem) showed a higher response in PTB than HHC; both ESAT-6 and Rv0009 showed similar positivity of 80% in PTB and 33% in HHC. PTB patients have a higher proportion of circulating antigen-reactive Tregs (CD4+CD25+FoxP3+) cell than LTBI. Rv2204c specific Tregs showed maximum positivity of 73% in PTB and 20% in HHC. Collectively, our data concludes that ESAT-6 specific Tcm and Rv2204c specific Tregs might be possible biomarkers useful to discriminate LTBI from active TB. This article is protected by copyright. All rights reserved.