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IL-2 immunotherapy in chronically SIV-infected Rhesus Macaques.
Garibal J., Laforge M., Silvestre R., Mouhamad S., Campillo-Gimenez L., Lévy Y., Estaquier J.
Virology Journal 9, 1 (2012) 220 - http://www.hal.inserm.fr/inserm-00752492
IL-2 immunotherapy in chronically SIV-infected Rhesus Macaques.
Julie Garibal1, Mireille Laforge2, Ricardo Silvestre3, Shahul Mouhamad1, Laure Campillo-Gimenez1, Yves Lévy () 1, 4, Jérôme Estaquier () 1, 5
1 :  Institut Mondor de Recherche Biomédicale
INSERM : U955 – Université Paris-Est Créteil Val-de-Marne (UPEC) – IFR10
8 rue du Général Sarrail, 94010 Créteil
2 :  Régulation de la transcription et maladies génétiques
CNRS : FRE3235 – Université Paris V - Paris Descartes
45 rue des Saints Pères 75270 Paris cedex 06
3 :  Instituto de Biologia Molecular e Celular
Universidade do Porto
Praça Gomes Teixeira, Porto 4099-002
4 :  Service d'Immunologie Clinique
Hôpital Henri Mondor – Assistance publique - Hôpitaux de Paris (AP-HP)
51, avenue du Mal de Lattre de Tassigny 94010 Créteil cedex
5 :  Centre de recherche en Infectiologie
Centre de Recherche en Infectiologie – Universite Laval (Quebec) - Canada
2325, rue de l'Université, Québec G1V 0A6
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.
Sciences du Vivant/Médecine humaine et pathologie/Maladies infectieuses

Articles dans des revues avec comité de lecture
Virology Journal
Publisher BioMed Central
ISSN 1743-422X 

SIV – IL-2 immunotherapy – T cells – Apoptosis – Fas – Treg
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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