PMID: identifiant
de la référence Pubmed : |
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 (23021024)  |
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| titre : |
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IL-2 immunotherapy in chronically SIV-infected Rhesus Macaques. |
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| auteur(s) : |
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Julie Garibal1, Mireille Laforge2, Ricardo Silvestre3, Shahul Mouhamad1, Laure Campillo-Gimenez1, Yves Lévy ( ) 1, 4, Jérôme Estaquier () 1, 5 |
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| laboratoire : |
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| résumé : |
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ABSTRACT: BACKGROUND: Despite inducing a sustained increase in CD4+ T cell counts, intermittent recombinant IL-2 (rIL-2) therapy did not confer a better clinical outcome in HIV-infected patients enrolled in large phase III clinical trials ESPRIT and SILCAAT. Several hypotheses were evoked to explain these discrepancies. Here, we investigated the impact of low and high doses of IL-2 in Rhesus macaques of Chinese origin infected with SIVmac251 in the absence of antiretroviral therapy (ART). RESULTS: We demonstrated that rIL-2 induced a dose dependent expansion of CD4+ and CD8+ T cells without affecting viral load. rIL-2 increased CD4 and CD8 Treg cells as defined by the expression of CD25highFoxP3+CD127low. We also showed that rIL-2 modulated spontaneous and Fas-mediated CD4+ and CD8+ T cell apoptosis. The higher dose exhibited a dramatic pro-apoptotic effect on both CD4+ and CD8+ T cell populations. Finally, all the animals treated with rIL-2 developed a wasting syndrome in the month following treatment simultaneously to a dramatic decrease of circulating effector T cells. CONCLUSION: These data contribute to the understanding of the homeostatic and dosage effects of IL-2 in the context of SIV/HIV infection. |
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| domaine : |
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Sciences du Vivant/Médecine humaine et pathologie/Maladies infectieuses
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langue du texte
intégral : |
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Anglais |
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| ISSN : |
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1743-422X |
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| type de publication : |
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Articles dans des revues avec comité de lecture |
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| DOI : |
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10.1186/1743-422X-9-220 |
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| journal : |
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| Audience : |
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internationale |
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| date de publication : |
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28/09/2012 |
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date de publication
électronique : |
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28/09/2012 |
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| volume : |
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9 |
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| numéro : |
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1 |
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| page, identifiant, ... : |
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220 |
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| mots-clés auteur : |
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SIV – IL-2 immunotherapy – T cells – Apoptosis – Fas – Treg |
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| contrat, financement : |
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This study was supported by research funding from the ANRS to JE and YL and the "Fondation pour la Recherche Médicale", to JE. JG and ML were supported by fellowships from ANRS, SM by SIDACTION and RS by a fellowship from the FCT program Ciência 2008. |
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