ENDOGENOUS TUMOR-NECROSIS-FACTOR-ALPHA CONTRIBUTES TO LYMPHOPROLIFERATION INDUCED BY SIMIAN IMMUNODEFICIENCY VIRUS VARIANT, SIVSMMPBJ14

The simian immunodeficiency virus (SIV) isolate, SIVsmmPBj14, contains an immunoreceptor tyrosine-based activation motif (ITAM) within its n ef gene product and triggers efficient lymphoproliferation in vitro. I n experimentally inoculated macaque monkeys, this virus causes acutely lethal enteropathy, which is accompanied by high levels of pro-inflam matory cytokines, including tumor necrosis factor (TNF)-alpha. Since T NF-alpha has been shown to possess weak comitogenic activity for antig en- or mitogen-induced human T-cell proliferation, experiments were co nducted to examine whether THF-alpha might also contribute to SIVsmmPB j14-induced lymphoproliferation. Addition of a dimeric soluble human T NF receptor (sTNFR):Fc fusion protein to SIVsmmPBj14-infected simian p eripheral blood mononuclear cells (PBMC) resulted in a partial (> 50%) inhibition of virally-induced lymphoproliferation, but had no effect on the strong T-cell activation signal provided by phytohemagglutinin and interleukin-2. Finally, the addition of exogenous human TNF-alpha to simian PBMC infected with a non-mitogenic variant of SIVsmmPBj14 fa iled to result in detectable lymphoproliferation, suggesting that TNF- alpha alone is not sufficient to cause the proliferation of SIV infect ed T-cells. Taken together, the data suggest that endogenous TNF-alpha enhances SIVsmmPBj14-induced lymphoproliferation in simian PBMC cultu res. (C) 1998 Elsevier Science B.V. All rights reserved.