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Published on: July 27, 2010
IL-10 producing CD8+ T cells in human infection with Leishmania guyanensis
Eliane Bourreau1, Catherine Ronet, Pierre Couppié
1Immunologie des Leishmanioses, Institut Pasteur de la Guyane, 97306 Cayenne, French Guiana.
Insights
This study reveals distinct cytokine profiles in Leishmania patients and healthy individuals. Transforming growth factor-beta (TGF-beta) neutralization in healthy subjects induced interleukin-10 (IL-10), impacting immune responses to Leishmania.
Area of Science:
- Immunology
- Cellular Biology
- Pathogen Response
Background:
- Cytokines are crucial in immune responses against intracellular pathogens.
- Leishmania infections elicit complex cellular immune reactions.
Purpose of the Study:
- To analyze cytokine production (TGF-beta, IL-10, IFN-gamma) in Leishmania-infected patients and healthy controls.
- To investigate the role of TGF-beta and IL-10 in modulating immune responses during Leishmania infection.
Main Methods:
- Peripheral blood mononuclear cells (PBMCs) from healthy subjects and LCL patients were stimulated with live Leishmania guyanensis.
- Cytokine production was measured, and TGF-beta was neutralized in vitro.
- Phenotypic analysis of cytokine-producing cells was performed using flow cytometry.
Main Results:
- IFN-gamma was produced by both controls and LCL patients.
- IL-10 was exclusively produced by LCL patients, while TGF-beta was produced by controls.
- TGF-beta neutralization in controls induced IL-10 production, primarily from CD8+ T cells.
- IL-10 inhibited reactive nitrogen species production without affecting IFN-gamma levels.
- In LCL patients, IL-10 was produced by both CD4+ and CD8+ T cells.
Conclusions:
- Distinct cytokine profiles differentiate Leishmania patients from healthy individuals.
- TGF-beta plays a regulatory role in IL-10 production by T cells.
- IL-10-producing CD8+ T cells may have a significant role in Leishmania pathogenesis and warrant further investigation.
Abstract:
Cytokines are increasingly recognized as important components of the cellular immune responses to intracellular pathogens. In this study, we analyzed the production of TGF-beta, IL-10 and IFN-gamma by PBMC of unexposed naïve subjects and LCL patients after stimulation with live Leishmania guyanensis (L.g.). We demonstrated that IFN-gamma is produced in controls and LCL patients, IL-10 only in LCL patients and TGF-beta only in naïve subjects. Furthermore, in naive subjects, neutralization of TGF-beta induced IL-10 production. IL-10 produced in naïve subjects when TGF-beta is neutralized or in LCL patients did not modify the IFN-gamma production but inhibit reactive nitrogen species production. Analysis of the phenotype of IL-10 producing cells in naive subjects when TGF-beta is neutralized clearly showed that they are memory CD45RA- CD8+ T cells. In LCL patients, IL-10 producing cells are both CD45RA- CD4 and CD8+ T cells. The role of these IL-10 producing CD8+ T cells in the development of the diseases should be carefully evaluated.
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