IL-2 immunotherapy in chronically SIV-infected Rhesus macaques
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Updated: May 18, 2026
Transduction and Expansion of Primary T Cells in Nine Days with Maintenance of Central Memory Phenotype
Published on: March 18, 2020
Julie Garibal1, Mireille Laforge, Ricardo Silvestre
1INSERM U955 Equipe 16, Institut Mondor de Recherche Biomédicale, Créteil, F-94010, France.
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 CD25(high)FoxP3(+)CD127(low). 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.
