Defective T Cell Function for Inhibition of Growth of Mycobacterium avium—intracellulare Complex (MAC) in Patients with MAC Disease: Restoration by Cytokines

2000 
+ T and gd T cells from patients were equally defective in inducing anti-MAC activity. The combination of these cytokines restored the ability of patients' T cells to control MAC growth. In experiments with allogeneic cocultures of gd T cells and infected monocytes from patients and control subjects, healthy control T cells could augment growth inhibition of MAC in monocytes from patients, whereas patients' T cells could not, even in the presence of healthy control monocytes. These results indicate that the defect in T cells may be associated with impaired protective immunity against MAC in these patients. Disseminated disease caused by Mycobacterium avium- intracellulare complex (MAC), which is often a fatal form of infection in patients with AIDS, has been on the decrease with the introduction of highly active antiretroviral therapy (1). Al- though the organisms, commonly found in soil, water, and house dust, are normally regarded as opportunistic bacterial pathogens, they also demonstrate pathogenicity at a localized pulmonary site in apparently normal persons without signs of systemic im- munologic diseases, including AIDS. The immunopathologic mechanism underlying pulmonary MAC disease in such patients without AIDS has not been well clarified. MAC can survive and even multiply within normal macrophages, and little is known about the mechanisms controlling these facultative intracellular bacteria. Most persons are very resistant to MAC. There is reportedly substantial variation in the inhibitory effect of cytokines on the growth of MAC, and it remains unclear whether a single cytokine or a combination of them renders macrophages mycobactericidal in humans. Interferon (IFN)-g induces mouse macrophages to inhibit MAC growth (2, 3), but, when tested alone in human macrophages, this cytokine may exhibit the opposite effect (4, 5). Macrophage colony-stimulating
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