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- Title
Retrovirus-elicited interleukin-12 and tumour necrosis factor-α as inducers of interferon-γ-mediated pathology in mouse AIDS.
- Authors
Giese, N. A.; Gazzinelli, R. T.; Actor, J. K.; Morawetz, R. A.; Sarzotti, M.; Morse III, H. C.
- Abstract
Spleen cells from mice resistant or sensitive to mouse acquired immune deficiency syndrome (MAIDS) were examined for cytokine mRNA. In MAIDS-resistant BALB/c mice, cytokine transcripts peaked at 1 week after infection with Type 1 cytokines [interleukin-2 (IL-2), turnout necrosis factor-α (TNF-α), interferon-γ (IFN-γ), IL-12], dominating over Type 2 cytokines (IL-4, IL-10). Expression of cytokines other than IL-2 later declined to levels seen in uninfected mice. In MAIDS-sensitive B6 mice, transcripts for all cytokines were increased at 1 week and, except for IL-2, increased progressively. Spontaneous production of IFN-γ protein was associated with enhanced mRNA expression at 1 week after infection of either strain, but none was detectable in association with even higher levels of transcripts at later times after infection of B6 mice. Spleen cells from longer-term-infected B6 mice, however, produced substantial amounts of IFN-γ following treatment with lipopolysaccharide (LPS) or IL-12. Inclusion of anti-IL-12 or anti- TNF-α antibodies blocked induction of IFN-γ by LPS. Induction of IFN-γ by IL-12 was potentiated by TNF-α following stimulation of intact spleen cells and purified CD4+ or CD8+ T cells, as well as negatively selected CD4-8- cells from infected B6 mice. Further studies showed that IFN-γ knockout mice on a B6 background developed MAIDS with a prolonged time-course, whereas BALB/c knockout mice were unchanged in their resistance to MAIDS. These studies suggest that continuing low-level expression of IFN-γ stimulated by IL-12 and TNF-α contributes to the susceptibility of B6 mice to MAIDS but is not required for the resistance of BALB/c mice to disease.
- Subjects
AIDS; LABORATORY mice; INTERLEUKIN-12; TUMOR necrosis factors; INTERFERONS; RETROVIRUSES; IMMUNOLOGY
- Publication
Immunology, 1996, Vol 87, Issue 3, p467
- ISSN
0019-2805
- Publication type
Article
- DOI
10.1046/j.1365-2567.1996.492569.x