Enhanced Peripheral Blood T lymphocyte Apoptosis in Pulmonary Tuberculosis: Correlation with Disease Severity as Reflected by Mycobacterial Load

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Background: Pulmonary tuberculosis (TB) is one of the major causes of illness and mortality worldwide. Control of TB requires coordinated efforts of both innate and adaptive immune systems. Apoptosis is a genetically regulated physiological process that when dysregulated can contribute to the pathogenesis of various diseases including TB. Objectives: The frequency of apoptotic T cells among peripheral blood mononuclear cells in patients with active pulmonary TB was studied and correlated with results of sputum bacterial load that reflects disease severity. Patients and methods: The study included 28 newly diagnosed tuberculin positive patients under anti-TB chemotherapy, classified into 3 groups according to sputum smear grading for AFB. In addition, 11 age matched apparently healthy individuals were included as a control group. PBMCs were stained for flowcytometric analysis using the TUNEL method. Results: Increased frequency of apoptotic T cells was observed in 71.4% of patients compared to controls. Patients with higher smear grades (grades 2+ and 3+) showed increased frequency of apoptosis compared to those with low smear grade (1+). Conclusion: Increased apoptosis may explain the T cell depletion/sustained low T cell responses observed in patients with active pulmonary TB. Its strong association with bacterial load make it a possible in vitro readout of pathogen burden that can be used for fast tracking the response to treatment. Targeting molecules involved in apoptosis may be an approach for an adjunctive anti-TB therapy that rescues T lymphocytes protective activity especially for infections caused by MDR and XDR MTB strains.

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