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.
Semenzato
G
G
Padua University School of Medicine, Institutes of Clinical Medicine and Oncology, Italy.
Agostini
C
C
Ometto
L
L
Zambello
R
R
Trentin
L
L
Chieco-Bianchi
L
L
De Rossi
A
A
D000163:Acquired Immunodeficiency Syndrome / Q000473:pathology / Q000821:virology*; D000328:Adult; D001992:Bronchoalveolar Lavage Fluid; D015704:CD4 Antigens / Q000096:biosynthesis; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism / Q000821:virology*; D002469:Cell Separation; D002478:Cells, Cultured; D004279:DNA, Viral / Q000032:analysis; D005260:Female; D015497:HIV-1 / Q000302:isolation & purification* / Q000502:physiology; D006801:Humans; D008168:Lung / Q000473:pathology / Q000821:virology*; D016676:Macrophages, Alveolar / Q000821:virology; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D016133:Polymerase Chain Reaction; D011533:Proviruses / Q000302:isolation & purification; D012333:RNA, Messenger / Q000032:analysis; D013602:T-Lymphocytes, Cytotoxic / Q000378:metabolism / Q000821:virology; D014779:Virus Replication
D015704:CD4 Antigens; D004279:DNA, Viral; D012333:RNA, Messenger