Old age-associated enrichment of peripheral T regulatory cells and altered redox status in pulmonary tuberculosis patients.

INTRODUCTION: Aging influences the susceptibility and prognosis to various infectious diseases including tuberculosis (TB). Despite the impairment of T cell function and immunity in geriatric individuals, the mechanism for the higher incidence of TB in the elderly remains largely unknown. Here we evaluated the age-associated immune alterations, particularly in effector and regulatory T cell responses in pulmonary TB patients. We also evaluated the impact of redox status and its modulation with N-acetyl-cysteine (NAC) in elderly TB. RESULTS: Higher frequency of Treg cells and reduced IFN-γ positive T cells were observed among older TB patients. Elevated number of Treg cells correlated tightly with bacillary load (i.e., disease severity); which declined significantly in response to successful anti-tubercular treatment. We could rescue M. tuberculosis-specific effector T cell (Th1) responses through various in vitro approaches viz., Treg cell depletion and co-culture experiments, blocking experiments using antibodies against IL-10, TGF-β and PD-1 as well as NAC supplementation. CONCLUSIONS: We report old age-associated enrichment of Treg cells and suppression of M. tuberculosis-specific effector T (Th1) cell immune responses. Monitoring these immune imbalances in older patients may assist in immune potentiation through selectively targeting Treg cells and/or optimizing redox status by NAC supplementation. This article is protected by copyright. All rights reserved.