Enhancement of HIV‐1 replication in human macrophages is induced by CD8+ T cell soluble factors

• Published in: Clinical and experimental immunology Vol. 114; no. 1; pp. 87 - 93
• Main Authors: COPELAND, K. F. T, MCKAY, P. J, NEWTON, J. J, ROSENTHAL, K. L
• Format: Journal Article
• Language: English
• Published: Oxford BSL Blackwell Science Ltd 01.10.1998; Blackwell; Blackwell Science Inc
• Subjects: AIDS/HIV; Biological and medical sciences; CD8+ T cell; CD8-Positive T-Lymphocytes - immunology; Culture Media, Conditioned; HIV; HIV-1 - physiology; Human viral diseases; Humans; Infectious diseases; macrophage; Macrophages - immunology; Macrophages - virology; Medical sciences; Original; Pertussis Toxin; replication; Transcription, Genetic; Viral diseases; Viral diseases of the lymphoid tissue and the blood. Aids; Virulence Factors, Bordetella; Virus Replication; Human; Immunopathology; Soluble factor; HIV-1 virus; Retroviridae; Helper cell; AIDS; Gene expression; Immune deficiency; Lentivirus; Host virus relation; Infection; Virus; Mixed cell culture; Viral disease; T-Lymphocyte; Replication; Human immunodeficiency virus
• ISSN: 0009-9104; 1365-2249
• DOI: 10.1046/j.1365-2249.1998.00699.x

We previously reported that CD8+ T cell‐derived factors enhanced HIV long terminal repeat (LTR)‐mediated gene expression and replication in monocytic cell lines. We now report that replication of NSI and SI primary isolates of HIV‐1 in human macrophages were significantly enhanced by CD8+ T cell supernatants. The CD8‐mediated enhancement of HIV replication was abrogated by pertussis toxin in a dose‐dependent manner. The sensitivity to pertussis toxin suggests that the CD8+ T cell‐derived enhancing factor is acting through a G protein‐coupled signalling pathway. Enhanced HIV replication in macrophages was accompanied by increased levels of HIV‐1 mRNA, suggesting that CD8 enhancement was mediated at the transcriptional level. Interestingly, the replication of HIVBal, which replicates to high levels in macrophages, was not significantly modulated by culture with CD8+ T cell supernatants. Although direct co‐culture of activated CD8+ T cells with HIVAda‐infected macrophages did not modulate replication, separation of the CD8+ T cells from macrophages in transwell cultures resulted in significant enhancement of replication. The inability to detect a modulatory effect in direct co‐cultures appeared to be due to non‐specific lysis of infected macrophages. Thus, soluble factors produced by CD8+ T cells exert strong enhancing effects on HIV‐1 replication in human macrophages.