Reduced NK activity in pulmonary tuberculosis patients with/without HIV infection: identifying the defective stage and studying the effect of interleukins on NK activity

Abstract

Setting: A study was undertaken to understand the non-major histocompatibility restricted cytotoxicity in order to delineate the role of natural killer (NK) cells towards the development of host immunity to tuberculosis.Objective: (a) Enumeration of NK cell numbers and activity in normal individuals (35), pulmonary tuberculosis patients (32), HIV-infected TB patients (20) and patient contacts (10), (b) effect of treatment on NK status, (c) enumeration of effector-target conjugates and (d) effect of in vitro cytokine stimulation on NK activity.Design: NK cells were enumerated by flowcytometry. NK activity was assessed by chromium release assay before and after treatment for tuberculosis and after stimulation with IL-2/IL-12. Novel flow cytometric method was standardized to enumerate effector-–target conjugates.Results: No changes were seen between different groups as far as number of NK cells and relative proportions of different conjugate types were concerned, but there was a decrease in NK activity in TB patients which increased after treatment. Augmentation of NK activity was observed after cytokine stimulation.Conclusion: Lowered NK activity during tuberculosis infection is probably the ‘effect’ and not the ‘cause’ for the disease as demonstrated by the follow-up study. Similar number of conjugates in both groups indicates no defect in the recognition/binding step but probably at subsequent steps of the cytotoxic process. Augmentation of NK activity with cytokines implicates them as potential adjuncts to tuberculosis chemotherapy.