Open Access Research

IL-2 immunotherapy in chronically SIV-infected Rhesus Macaques

Julie Garibal1, Mireille Laforge4, Ricardo Silvestre6, Shahul Mouhamad1, Laure Campillo-Gimenez1, Yves Lévy123* and Jérôme Estaquier15*

Author Affiliations

1 INSERM U955 Equipe 16, Institut Mondor de Recherche Biomédicale, Créteil, F-94010, France

2 Université Paris-Est, Faculté de Médecine, UMR-S 955, Créteil, F-94010, France

3 Assistance Publique-Hôpitaux de Paris (AP-HP), Groupe Henri-Mondor Albert-Chenevier, service d’immunologie clinique, Créteil, F-94010, France

4 CNRS FRE 3235, Université Paris Descartes, Paris, France

5 Université Laval, Centre de recherche en Infectiologie, Québec, Canada

6 Instituto de Biologia Molecular e Celular, Universidade do Porto, Porto, Portugal

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Virology Journal 2012, 9:220  doi:10.1186/1743-422X-9-220

Published: 28 September 2012

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