The Journal of Immunology, Vol 144, Issue 3 970-975, Copyright © 1990 by American Association of Immunologists

ARTICLES

Differential gene expression of IFN-alpha and tumor necrosis factor- alpha in peripheral blood mononuclear cells from patients with AIDS related complex and AIDS

R Voth, S Rossol, K Klein, G Hess, KH Schutt, HC Schroder, KH Meyer zum Buschenfelde and WE Muller
Medizinische Klinik and Poliklinik, Klinikum der Universitat, Mainz, West Germany.

Human PBMC from HIV-1-infected individuals produced ex vivo in response to vesicular stomatitis virus only low amounts of IFN-alpha. This impairment was significant as early as Walter Reed (WR) stage 2; at WR stage 4-5, the production was almost zero. At WR stage 2 of infection, IFN-alpha mRNA was exclusively found in association with polyribosomes, indicating that IFN-alpha gene was transcriptionally inactive under the experimental conditions used. A similar decrease of the level of transcripts as a function of the progression of the disease was also observed for the IFN-gamma mRNA. In contrast, TNF-alpha production was strongly enhanced in PBMC from HIV-1-infected individuals after stimulation with LPS compared to the TNF-alpha production of activated PBMC from healthy donors. Almost parallel with the increase of the level of the transcript for TNF-alpha, the level of TNF-beta increases as well. Data are presented which show that the increased TNF-alpha production is due to a longer half-life of TNF-alpha transcripts in PBMC from infected individuals. These results let us suggest that the up-regulation of TNF-alpha gene expression in PBMC from HIV-infected individuals is controlled predominantly on the posttranscriptional level, whereas transcriptional events regulate the level of IFN-alpha transcripts. This assumption is supported by run-on experiments which revealed that the extent of transcription of TNF-alpha gene is almost identical in nuclei from stimulated PBMC of noninfected and HIV- infected donors, whereas the transcription of IFN-alpha gene is strongly suppressed in nuclei from HIV-infected individuals at WR stages 3 and 6.

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