Cytotoxic Events Taking Place in the Lung of Patients with HIV-1 Infection: Evidence of an Intrinsic Defect of the Major Histocompatibility Complex-unrestricted Killing Partially Restored by the Incubation with rIL-2

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Abstract
To characterize the cytotoxic events taking place in the lung of patients with HIV-1 infection, we studied the cells recovered from the bronchoalveolar lavage (BAL) of nine patients with AIDS, seven patients with AIDS-related complex, and two patients with lymphadenopathy. Phenotypic analysis was coupled to a series of functional evaluations of nonspecific cytotoxic abilities performed on lung effectors, including their property to bind K-562 targets, to release natural killer cytotoxic factor (NKCF), and to become cytotoxic following in vitro activation with rIL-2. Our results demonstrated that lung cells bearing the NK-related CD16, CD56, and CD57 antigens were quantitatively increased, irrespective of the disease stage. The majority of the cells also coexpressed the CD3 molecule and the α/β T cell receptor (TCR), notably the phenotype characterizing MHC-unrestricted cytotoxic T cells. From a functional point of view, a severe impairment of the spontaneous cytotoxic ability was demonstrated in most patients. Evaluation at the single cell level showed a normal percentage of the effector/target conjugates formed by HIV-1 lymphocytes. The release of NKCF was undetectable in patients with AIDS even following lectin stimulation, whereas BAL cells from patients with earlier infection produced and/or could be triggered to release discrete amounts of NKCF by incubation with PHA. Studies designed to activate lung cytotoxic cells with rIL-2 showed that in most patients the stimulation of effector cells with rIL-2 enhanced the spontaneous killing and elicited a lymphokine-activated killer (LAK) phenomenon. Taken together, these data suggest that the defective spontaneous cytotoxicity observed in lung cells from AIDS patients was not due to their inability to bind the targets but was consequent to their failure to release the soluble molecule (NKCF), which is mandatory for the efficiency of the cytotoxic machinery. The possibility of triggering the cytotoxic ability of lung cells with rIL-2 suggests that pulmonary MHC-unrestricted effectors may be modulated via IL-2 receptors.