TUMOR-NECROSIS-FACTOR-ALPHA INCREASES THE SENSITIVITY OF HUMAN-IMMUNODEFICIENCY-VIRUS (HIV)-INFECTED MONOCYTIC U937 CELLS TO THE COMPLEMENT-DEPENDENT CYTOTOXICITY OF SERA FROM HIV TYPE-1-INFECTED INDIVIDUALS -ROLE OF THE GP120 PROTEIN

Sera of 40 intravenous drug addicts [25 seropositive and 15 seronegati ve for human immunodeficiency virus (HIV)] were tested for the presenc e of cytotoxic antibodies against uninfected and HIV-infected monocyti c U937 cells. Six of the 25 seropositive samples proved to be cytotoxi c for HIV-infected target cells in the presence of complement. The pre treatment of HIV-infected U937 cells with tumour necrosis factor (TNF) -alpha (which enhances virus production in these cells) increased the detection of serum cytotoxicity and 60 % of these sera became cytotoxi c. The percentage lysis was also increased after the TNF-alpha treatme nt of the target cells (from 16.2 +/- 4.5 to 71.2 +/- 4.9). The comple ment-dependent cytotoxic activity of these sera was significantly redu ced by pretreatment with recombinant HIV gp120 antigen. This reduction was dose-dependent in the majority of cases. Immunofluorescence studi es suggested that the cytotoxic sera mainly interacted with the viral antigens localized on the membrane of HIV-infected TNF-treated U937 ce lls. Moreover, comparative Western blot analyses using cellular extrac ts from untreated and TNF-treated U937 cells showed that there was a p ositive correlation between the cytotoxic phenotype and the capacity o f sera to recognize the gp120 protein in extracts from TNF-treated HIV -infected cells. These results suggest that in some circumstances endo genous TNF-alpha can be a protective factor because it can render pers istently infected cells highly sensitive to complement-dependent serum cytotoxicity as a result of increased expression of the relevant vira l antigen (gp120) on the cell membrane.