Mycobacterium tuberculosisGrowth Control by Lung Macrophages and CD8 Cells from Patient Contacts

Abstract

Healthy household contacts (HHCs) of patients with active pulmonary tuberculosis are exposed aerogenically to Mycobacterium tuberculosis (Mtb), thus permitting the study of protective local immunity. To assess alveolar macrophage (AM) and autologous blood CD4 and CD8 T-cell-mediated Mtb growth control in HHCs and healthy, unexposed community control subjects (CCs). AMs were infected with Mtb strains H(37)Ra and H(37)Rv at multiplicities of infection 0.1 and 1. Mtb colony-forming units were evaluated on Days 1, 4, and 7. CD8 T cells from HHCs in 1:1 cocultures with AMs significantly (p < 0.05) increased Mtb growth control by AMs. In CCs, no detectable contribution of CD8 T cells to Mtb growth control was observed. CD4 T cells did not increase Mtb growth control in HHCs or in CCs. IFN-gamma, nitric oxide, and tumor necrosis factor were determined as potential mediators of Mtb growth control in AMs and AM/CD8 and AM/CD4 cocultures. IFN-gamma production in AM/CD4 was twofold higher than that in AM/CD8 cocultures in both HHCs and CCs (p < 0.05). Nitric oxide production from AMs of HHCs increased on Days 4 and 7 and was undetectable in AMs from CCs. IFN-gamma and nitric acid concentrations and Mtb growth control were not correlated. Tumor necrosis factor levels were significantly increased in AM/CD8 cocultures from HHCs compared with AM/CD8 cocultures from CCs (p < 0.05). Aerogenic exposure to Mtb in HHCs leads to expansion of Mtb-specific effector CD8 T cells that limit Mtb growth in autologous AMs.