title: Interleukin-7 treatment counteracts IFN-α therapy-induced lymphopenia and stimulates SIV-specific cytotoxic T lymphocyte responses in SIV-infected rhesus macaques.
abstract: Interferon-α (IFN-α)-based therapy is presently the standard treatment for hepatitis C virus (HCV)-infected patients. Despite good effectiveness, this cytokine is associated with major side effects, including significant lymphopenia, that limits its use for HIV/HCV-coinfected patients. Interleukin-7 (IL-7) has recently shown therapeutic potential and safety in several clinical trials designed to demonstrate T-cell restoration in immunodeficient patients. The purpose of this study was to evaluate, in simian immunodeficiency virus-infected rhesus macaques, the relevance of IL-7 therapy as a means to overcoming IFN-α-induced lymphopenia. We showed that low-dose IFN-α treatment induced strong lymphopenia in chronically infected monkeys. In contrast, high-dose IFN-α treatment stimulated IL-7 production, leading to increased circulating T-cell counts. Moreover, IL-7 therapy more than abrogated the lymphopenic effect of low-dose IFN-α. Indeed, the association of both cytokines resulted in increased circulating T-cell counts, in particular in the naive compartments, as a consequence of central and peripheral homeostatic functions of the IL-7. Finally, reduced PD-1 expression by memory CD8(+) T cells and transient T-cell repertoire diversification were observed under IL-7 therapy. Our data strongly suggest that IL-7 immunotherapy will be of substantial benefit in the treatment of HIV/HCV coinfection and should enhance the likelihood of HCV eradication in poorly responding patients.
authors.affiliation: Département de Virologie, Institut Pasteur, Paris, France.
authors.forename: Raphaëlle
authors.initials: R
authors.lastname: Parker
authors.forename: Jacques
authors.initials: J
authors.lastname: Dutrieux
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Beq
authors.forename: Brigitte
authors.initials: B
authors.lastname: Lemercier
authors.forename: Sandra
authors.initials: S
authors.lastname: Rozlan
authors.forename: Véronique
authors.initials: V
authors.lastname: Fabre-Mersseman
authors.forename: Magali
authors.initials: M
authors.lastname: Rancez
authors.forename: Céline
authors.initials: C
authors.lastname: Gommet
authors.forename: Brigitte
authors.initials: B
authors.lastname: Assouline
authors.forename: Iann
authors.initials: I
authors.lastname: Rancé
authors.forename: Annick
authors.initials: A
authors.lastname: Lim
authors.forename: Michel
authors.initials: M
authors.lastname: Morre
authors.forename: Rémi
authors.initials: R
authors.lastname: Cheynier
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000627:therapeutic use*; D005434:Flow Cytometry; D006801:Humans; D007156:Immunologic Memory; D016898:Interferon-alpha / Q000627:therapeutic use*; D015851:Interleukin-7 / Q000627:therapeutic use*; D008213:Lymphocyte Activation / Q000187:drug effects; D008231:Lymphopenia / Q000139:chemically induced / Q000188:drug therapy*; D008253:Macaca mulatta; D016097:Simian Acquired Immunodeficiency Syndrome / Q000188:drug therapy* / Q000276:immunology; D015302:Simian Immunodeficiency Virus / Q000276:immunology*; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D019562:Viral Load
chemical_list: D000998:Antiviral Agents; D016898:Interferon-alpha; D015851:Interleukin-7