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: Raphaëlle Parker, Jacques Dutrieux, Stéphanie Beq, Brigitte Lemercier, Sandra Rozlan, Véronique Fabre-Mersseman, Magali Rancez, Céline Gommet, Brigitte Assouline, Iann Rancé, Annick Lim, Michel Morre, Rémi Cheynier
• Journal: Blood (Blood) Vol. 116 Issue 25 Pg. 5589-99 (Dec 16 2010) ISSN: 1528-0020 [Electronic] United States
• PMID: 20841508 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antiviral Agents
• Interferon-alpha
• Interleukin-7

Topics

• Animals
• Antiviral Agents (therapeutic use)
• Flow Cytometry
• Humans
• Immunologic Memory
• Interferon-alpha (therapeutic use)
• Interleukin-7 (therapeutic use)
• Lymphocyte Activation (drug effects)
• Lymphopenia (chemically induced, drug therapy)
• Macaca mulatta
• Simian Acquired Immunodeficiency Syndrome (drug therapy, immunology)
• Simian Immunodeficiency Virus (immunology)
• T-Lymphocytes (cytology, drug effects, immunology)
• T-Lymphocytes, Cytotoxic (immunology)
• Viral Load