Stimulation of bystander T-cell proliferation by tumor necrosis factor produced by HIV-1-infected macrophages.
OBJECTIVE
Cocultivation of the CD4+CD95+ T-cell line (MT4) with monocyte-derived macrophages (MDMs) infected with the HIV-1 resulted in costimulation of proliferation and apoptosis after 20 hours of contact. This study sought to determine whether tumor necrosis factor (TNF) produced by HIV-1-infected MDMs was involved in the costimulation of cell proliferation, the apoptotic pathway, or both.


METHODS
MT4 cells were cocultivated with infected or noninfected MDMs in the presence or absence of soluble TNF receptors (sTNFRs) or antagonistic anti-Fas antibody (ZB4). Cell proliferation was assessed by measuring thymidine incorporation. Apoptosis was monitored by using flow cytometry and enzyme-linked immunosorbent assay (ELISA).


RESULTS
Thymidine incorporation was higher in cells cocultivated with HIV-infected or noninfected MDMs than it was in controls grown in culture medium. It also was higher in cells cocultivated with HIV-infected MDMs than it was in cells cocultivated with noninfected MDMs. sTNFRs blocked the increase of thymidine incorporation specifically induced by HIV-infected MDMs. They did not inhibit apoptosis at 20 hours. Cells recovered from cocultures involving HIV-infected or noninfected MDMs exhibited decreased sensitivity to apoptosis induced through the Fas receptor.


CONCLUSIONS
TNF produced by HIV-infected MDMs acts as an accessory T-cell growth factor that synergizes with an as yet unidentified growth-inducing signal or signals produced by HIV-infected and noninfected MDMs. Stimulation of cell proliferation by MDMs induces transient resistance to Fas-induced apoptosis.
Godard
C M
CM
Unité de Recherche sur les Rétrovirus et Maladies Associées, Parc Scientifique et Technologique de Luminy, Marseille, France. u322@inserm-nacre.univ-mrs.fr
Chermann
J C
JC
D017209:Apoptosis / Q000502:physiology*; D015704:CD4 Antigens / Q000378:metabolism; D002455:Cell Division; D002460:Cell Line; D018920:Coculture Techniques / Q000379:methods; D015497:HIV-1; D006801:Humans; D008264:Macrophages / Q000378:metabolism / Q000821:virology*; D013601:T-Lymphocytes / Q000166:cytology*; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism / Q000502:physiology*; D019014:fas Receptor / Q000378:metabolism
D015704:CD4 Antigens; D014409:Tumor Necrosis Factor-alpha; D019014:fas Receptor