Retrovirus-elicited interleukin-12 and tumour necrosis factor-alpha as inducers of interferon-gamma-mediated pathology in mouse AIDS
| Autor: | Herbert C. Morse, N.A. Giese, Ricardo T. Gazzinelli, Marcella Sarzotti, Jeffrey K. Actor, R.A. Morawetz |
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| Rok vydání: | 1996 |
| Předmět: |
Lipopolysaccharides
Pathology medicine.medical_specialty Necrosis Lipopolysaccharide medicine.medical_treatment T-Lymphocytes Immunology Spleen Biology Polymerase Chain Reaction chemistry.chemical_compound Interferon-gamma Mice Murine Acquired Immunodeficiency Syndrome medicine Immunology and Allergy Animals Interferon gamma Mice Knockout Mice Inbred BALB C Tumor Necrosis Factor-alpha Interleukin-12 Immunity Innate Interleukin-10 Mice Inbred C57BL Cytokine medicine.anatomical_structure chemistry Knockout mouse Interleukin 12 Interleukin-2 Female Interleukin-4 medicine.symptom CD8 medicine.drug Research Article |
| Zdroj: | Immunology. 87(3) |
| ISSN: | 0019-2805 |
| Popis: | 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), tumour necrosis factor-alpha (TNF-alpha), interferon-gamma (IFN-gamma), 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-gamma 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-gamma following treatment with lipopolysaccharide (LPS) or IL-12. Inclusion of anti-IL-12 or anti-TNF-alpha antibodies blocked induction of IFN-gamma by LPS. Induction of IFN-gamma by IL-12 was potentiated by TNF-alpha 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-gamma 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-gamma, stimulated by IL-12 and TNF-alpha, contributes to the susceptibility of B6 mice to MAIDS but is not required for the resistance of BALB/c mice to disease. |
| Databáze: | OpenAIRE |
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