Interleukin-7 treatment counteracts IFN-α therapy-induced lymphopenia and stimulates SIV-specific cytotoxic T lymphocyte responses in SIV-infected rhesus macaques.
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.
Parker
Raphaëlle
R
Département de Virologie, Institut Pasteur, Paris, France.
Dutrieux
Jacques
J
Beq
Stéphanie
S
Lemercier
Brigitte
B
Rozlan
Sandra
S
Fabre-Mersseman
Véronique
V
Rancez
Magali
M
Gommet
Céline
C
Assouline
Brigitte
B
Rancé
Iann
I
Lim
Annick
A
Morre
Michel
M
Cheynier
Rémi
R
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
D000998:Antiviral Agents; D016898:Interferon-alpha; D015851:Interleukin-7