Enhancement of HIV-1 replication in human macrophages is induced by CD8+ T cell soluble factors.
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 HIV(Bal), 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 HIV(Ada)-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.
Copeland
K F
KF
Department of Pathology, McMaster University Health Sciences Centre, Hamilton, Ontario, Canada.
McKay
P J
PJ
Newton
J J
JJ
Rosenthal
K L
KL
D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D017077:Culture Media, Conditioned; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D008264:Macrophages / Q000276:immunology / Q000821:virology*; D037342:Pertussis Toxin; D014158:Transcription, Genetic; D010566:Virulence Factors, Bordetella; D014779:Virus Replication
D017077:Culture Media, Conditioned; D010566:Virulence Factors, Bordetella; D037342:Pertussis Toxin