title: IL-2 immunotherapy in chronically SIV-infected Rhesus macaques.
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 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.
  
  
  CONCLUSIONS
  These data contribute to the understanding of the homeostatic and dosage effects of IL-2 in the context of SIV/HIV infection.
authors.affiliation: INSERM U955 Equipe 16, Institut Mondor de Recherche Biomédicale, Créteil, F-94010, France.
authors.forename: Julie
authors.initials: J
authors.lastname: Garibal
authors.forename: Mireille
authors.initials: M
authors.lastname: Laforge
authors.forename: Ricardo
authors.initials: R
authors.lastname: Silvestre
authors.forename: Shahul
authors.initials: S
authors.lastname: Mouhamad
authors.forename: Laure
authors.initials: L
authors.lastname: Campillo-Gimenez
authors.forename: Yves
authors.initials: Y
authors.lastname: Lévy
authors.forename: Jérôme
authors.initials: J
authors.lastname: Estaquier
mesh_terms: D000818:Animals; D017209:Apoptosis; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D004195:Disease Models, Animal; D007155:Immunologic Factors / Q000008:administration & dosage*; D007167:Immunotherapy / Q000379:methods; D007376:Interleukin-2 / Q000008:administration & dosage*; D018655:Lymphocyte Count; D008253:Macaca mulatta; D016097:Simian Acquired Immunodeficiency Syndrome / Q000628:therapy*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D016896:Treatment Outcome; D019562:Viral Load
chemical_list: D007155:Immunologic Factors; D007376:Interleukin-2