HIV infection of monocytes inhibits the T-lymphocyte proliferative response to recall antigens, via production of eicosanoids.
Human monocytes infected in vitro with human immunodeficiency virus (HIV) soon after adherence to plastic substrate demonstrated a significantly decreased ability to restimulate autologous immune T-lymphocyte proliferation after exposure to soluble (tetanus toxoid) and particulate [herpes simplex virus (HSV)] antigen. Incubation with the cyclo-oxygenase inhibitor, indomethacin (2-5 microM), prevented inhibition of antigen-stimulated lymphocyte proliferation. The inhibitory activity was identified in ultrafiltrates containing the low molecular weight fraction (less than 3000 MW) of supernatants from HIV-infected monocyte cultures. This activity was significantly and markedly reduced in similar ultrafiltrates prepared from indomethacin-treated cultures. Increased concentrations of prostaglandin E2 (PGE2) were detected in ultrafiltrates from HIV-infected monocyte cultures compared with uninfected cultures and cultures preincubated with indomethacin. Ultrafiltrates were inhibitory when added during the presentation of antigen to T lymphocytes but not when removed from monocyte cultures prior to the addition of lymphocytes. In addition, ultrafiltrates inhibited antigen-stimulated lymphocyte proliferation and PHA-induced lymphocyte proliferation to the same extent. These data indicate that cyclo-oxygenase products of arachidonic acid, including PGE2, are produced in excess by HIV-infected monocytes and that PGE2 and perhaps other cyclo-oxygenase products are implicated in the inhibition of antigen-stimulated lymphocyte proliferation via a direct effect on T lymphocytes.
Foley
P
P
Centre for Infectious Diseases and Microbiology, University of Sydney, Westmead Hospital, New South Wales, Australia.
Kazazi
F
F
Biti
R
R
Sorrell
T C
TC
Cunningham
A L
AL
D002455:Cell Division / Q000276:immunology; D002478:Cells, Cultured; D015232:Dinoprostone / Q000276:immunology; D015777:Eicosanoids / Q000276:immunology*; D015658:HIV Infections / Q000276:immunology*; D006801:Humans; D007108:Immune Tolerance / Q000276:immunology*; D008264:Macrophages / Q000276:immunology; D009000:Monocytes / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*; D013745:Tetanus Toxoid / Q000276:immunology
D015777:Eicosanoids; D013745:Tetanus Toxoid; D015232:Dinoprostone