CD8(+) T-LYMPHOCYTES IN THE LUNG OF ACQUIRED-IMMUNODEFICIENCY-SYNDROME PATIENTS HARBOR HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1

Human immunodeficiency virus-1 (HIV-1) infection of CD8(+) lymphocytes has been described in several in vitro culture systems, but whether CD8(+) cells are a target and also serve as a reservoir for infection in vivo as yet is unknown. We addressed this issue in patients with acquired immunodeficiency syndrome (AIDS)-related lower respiratory tract chronic inflammation, which is characterized by a massive influx of CD8(+) HIV-1-specific cytotoxic T lymphocytes (CTL). Proviral load in lung T lymphocytes and their subpopulations was evaluated by using the DNA-polymerase chain reaction (PCR) technique on cells retrieved by bronchoalveolar lavage. To avoid the possibility that the presence of HIV-1 DNA could be caused by contaminating CD4(+) cells, serial dilutions of highly purified CD8(+) cells were also analyzed by PCR. Our findings showed that lung CD8(+) cells harbor and express HIV-1. To explore the possible mechanisms leading to pulmonary CD8(+) lymphocyte infection, we evaluated CD4 gene expression on highly purified CD8(+) cells by means of reverse transcriptase PCR, Despite the lack of membrane CD4 reactivity, we could show that CD8(+) cells may express CD4 RNA, Coinfection of lung CD8(+) cells harboring proviral HIV-1 sequences by viral agents capable of inducing CD4 expression (ie, HHV-6) was not detected. Our data indicate that not only CD4(+) T lymphocytes and macrophages, but also CD8(+) cells, may represent a target and/or a reservoir for HIV-1 in vivo, and suggest that lung CD8(+) lymphocytes could derive from precursors equipped with enough CD4 molecules to become HIV-1 permissive, Aside from the cell-to-cell contact between activated HIV-1 specific CTL and relevant targets, the infection of precursors could represent an additional mechanism accounting for the infection of pulmonary CD8(+) cells and their functional impairment. (C) 1995 by The American Society of Hematology.