HIV-specific cytotoxic T lymphocytes directed against alveolar macrophages in HIV-infected patients

Abstract

A CD8+ lymphocytic infiltration of the lungs is frequently observed in HIV-infected patients, even prior to the onset of opportunistic infections. In such patients, we could demonstrate that most of these CD8+ alveolar T lymphocytes displayed the D44 marker and were functional cytolytic T lymphocytes directed against autologous HIV-infected alveolar macrophages. This primary cytolytic activity was HLA-restricted and, at least partially, specific for the HIV envelope protein, since HLA-A2 alveolar T lymphocytes could specifically lyse cell lines expressing both the HLA-A2 and Env antigens. In contrast to data obtained in peripheral blood, no ADCC activity was observed against the Env antigen. HIV-specific alveolar T-lymphocyte cytolytic activity decreased with progression towards AIDS as shown by studies of a series of 40 patients. Functional abnormalities of the lung epithelium could be associated with the specific lysis of alveolar macrophages, suggesting that local tissue injury could result from the in vivo immune conflict between alveolar HIV-specific CTL and HIV-infected macrophages.