title: IL-7 induces immunological improvement in SIV-infected rhesus macaques under antiviral therapy.
abstract: Despite efficient antiretroviral therapy (ART), CD4+ T cell counts often remain low in HIV-1-infected patients. This has led to IL-7, a crucial cytokine involved in both thymopoiesis and peripheral T cell homeostasis, being suggested as an additional therapeutic strategy. We investigated whether recombinant simian IL-7-treatment enhanced the T cell renewal initiated by ART in rhesus macaques chronically infected with SIVmac251. Six macaques in the early chronic phase of SIV infection received antiretroviral treatment. Four macaques also received a 3-wk course of IL-7 injections. Viral load was unaffected by IL-7 treatment. IL-7 treatment increased the number of circulating CD4+ and CD8+ memory T cells expressing activation (HLA-DR+, CD25+) and proliferation (Ki-67+) markers. It also increased naive (CD45RAbrightCD62L+) T cell counts by peripheral proliferation and enhanced de novo thymic production. The studied parameters returned to pretreatment values by day 29 after the initiation of treatment, concomitantly to the appearance of anti-IL-7 neutralizing Abs, supporting the need for a nonimmunogenic molecule for human treatment. Thus, IL-7, which increases T cell memory and de novo renewal of naive T cells may have additional benefits in HIV-infected patients receiving ART.
authors.affiliation: Unité de Régulation des Infections Rétrovirales, Institut Pasteur, Paris, France.
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Beq
authors.forename: Marie-Thérèse
authors.initials: MT
authors.lastname: Nugeyre
authors.forename: Raphaël
authors.initials: R
authors.lastname: Ho Tsong Fang
authors.forename: David
authors.initials: D
authors.lastname: Gautier
authors.forename: Roger
authors.initials: R
authors.lastname: Legrand
authors.forename: Nathalie
authors.initials: N
authors.lastname: Schmitt
authors.forename: Jérôme
authors.initials: J
authors.lastname: Estaquier
authors.forename: Françoise
authors.initials: F
authors.lastname: Barré-Sinoussi
authors.forename: Bruno
authors.initials: B
authors.lastname: Hurtrel
authors.forename: Rémi
authors.initials: R
authors.lastname: Cheynier
authors.forename: Nicole
authors.initials: N
authors.lastname: Israël
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000627:therapeutic use*; D001483:Base Sequence; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D049109:Cell Proliferation / Q000187:drug effects; D004247:DNA / Q000235:genetics; D006801:Humans; D015851:Interleukin-7 / Q000276:immunology / Q000494:pharmacology*; D008213:Lymphocyte Activation / Q000187:drug effects; D018655:Lymphocyte Count; D008253:Macaca mulatta; D011994:Recombinant Proteins / Q000276:immunology / Q000494:pharmacology; D016097:Simian Acquired Immunodeficiency Syndrome / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology* / Q000821:virology; D016176:T-Lymphocyte Subsets / Q000187:drug effects* / Q000276:immunology; D014766:Viremia / Q000188:drug therapy / Q000276:immunology / Q000821:virology
chemical_list: D000998:Antiviral Agents; D015851:Interleukin-7; D011994:Recombinant Proteins; D004247:DNA