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IL-12 enhances Th1-type responses in human Leishmania donovani infections.
- Source :
-
Journal of immunology (Baltimore, Md. : 1950) [J Immunol] 1995 May 01; Vol. 154 (9), pp. 4623-9. - Publication Year :
- 1995
-
Abstract
- IL-12 is a pluripotent cytokine that interacts with NK and T cells to play a central role in the initiation and maintenance of Th1 responses and IFN-gamma production. Because of the interactive relationship between IL-12 and IFN-gamma response to infectious organisms, a study was undertaken to examine the role of IL-12 in the immune regulation of human visceral leishmaniasis (VL). Human (Hu) VL is associated with immune dysfunction and the appearance of IL-10 mRNA, not present in healed individuals. We found that PBMC from treated VL patients produced both IL-12 p40 and IFN-gamma in response to in vitro stimulation with Leishmania donovani. The production of both IL-12 p40 and IFN-gamma were interdependent and were abrogated by the addition of exogenous Hu rIL-10. In contrast, PBMC from active VL patients did not produce IL-12 p40 or IFN-gamma in response to L. donovani lysate. Neutralizing anti-IL-10 mAb led to the enhancement of IFN-gamma production by active VL PBMC cultured with L. donovani lysate, and this enhanced IFN-gamma production was blocked by anti-IL-12 mAb. The addition of exogenous Hu rIL-12 to PBMC from active VL patients resulted in the augmentation of IFN-gamma in response to L. donovani lysate. Therefore, treatment of active VL patient PBMC with anti-IL-10 or IL-12 shifted the response toward a Th1-type response with the production of IFN-gamma. These results indicate that IL-12 may play an important role in the regulation of the cellular immune responses in Hu VL.
- Subjects :
- Animals
Antibodies, Monoclonal immunology
Cells, Cultured
Enzyme-Linked Immunosorbent Assay
Humans
Interferon-gamma biosynthesis
Interleukin-10 immunology
Lymphocyte Activation immunology
Interleukin-12 biosynthesis
Interleukin-12 immunology
Leishmania donovani immunology
Leishmaniasis, Visceral immunology
Th1 Cells immunology
Subjects
Details
- Language :
- English
- ISSN :
- 0022-1767
- Volume :
- 154
- Issue :
- 9
- Database :
- MEDLINE
- Journal :
- Journal of immunology (Baltimore, Md. : 1950)
- Publication Type :
- Academic Journal
- Accession number :
- 7722314