IL-2 immunotherapy in chronically SIV-infected Rhesus Macaques.

Julie Garibal 1 Mireille Laforge 2 Ricardo Silvestre 3 Shahul Mouhamad 1 Laure Campillo-Gimenez 1 Yves Lévy 1, 4, * Jérôme Estaquier 1, 5, *
* Auteur correspondant
1 IMRB - Institut Mondor de Recherche Biomédicale
2 Régulation de la transcription et maladies génétiques
3 Instituto de Biologia Molecular e Celular
4 Service d'immunologie clinique [Créteil]
5 Centre de recherche en Infectiologie
Abstract : 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.
Keywords : SIV IL-2 immunotherapy T cells Apoptosis Fas Treg
Type de document :
Article dans une revue
Virology Journal, BioMed Central, 2012, 9 (1), pp.220. 〈10.1186/1743-422X-9-220〉
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http://www.hal.inserm.fr/inserm-00752492
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Soumis le : jeudi 15 novembre 2012 - 21:10:32
Dernière modification le : jeudi 11 janvier 2018 - 06:25:25
Document(s) archivé(s) le : samedi 17 décembre 2016 - 11:06:00

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Julie Garibal, Mireille Laforge, Ricardo Silvestre, Shahul Mouhamad, Laure Campillo-Gimenez, et al.. IL-2 immunotherapy in chronically SIV-infected Rhesus Macaques.. Virology Journal, BioMed Central, 2012, 9 (1), pp.220. 〈10.1186/1743-422X-9-220〉. 〈inserm-00752492〉

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