title: Altered thymic function during interferon therapy in HCV-infected patients.
abstract: Interferon alpha (IFNα) therapy, despite good efficacy in curing HCV infection, leads to major side effects, in particular inducement of a strong peripheral T-cell lymphocytopenia. We here analyze the early consequences of IFNα therapy on both thymic function and peripheral T-cell homeostasis in patients in the acute or chronic phase of HCV-infection as well as in HIV/HCV co-infected patients. The evolution of T-cell subsets and T-cell homeostasis were estimated by flow cytometry while thymic function was measured through quantification of T-cell receptor excision circles (TREC) and estimation of intrathymic precursor T-cell proliferation during the first four months following the initiation of IFNα therapy. Beginning with the first month of therapy, a profound lymphocytopenia was observed for all T-cell subsets, including naïve T-cells and recent thymic emigrants (RTE), associated with inhibition of intrathymic precursor T-cell proliferation. Interleukin (IL)-7 plasma concentration rapidly dropped while lymphocytopenia progressed. This was neither a consequence of higher consumption of the cytokine nor due to its neutralization by soluble CD127. Decrease in IL-7 plasma concentration under IFNα therapy correlated with the decline in HCV viral load, thymic activity and RTE concentration in blood. These data demonstrate that IFNα-based therapy rapidly impacts on thymopoiesis and, consequently, perturbs T-cell homeostasis. Such a side effect might be detrimental for the continuation of IFNα therapy and may lead to an increased level of infectious risk, in particular in HIV/HCV co-infected patients. Altogether, this study suggests the therapeutic potential of IL-7 in the maintenance of peripheral T-cell homeostasis in IFNα-treated patients.
authors.affiliation: Département de Virologie, Institut Pasteur, Paris, France.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Beq
authors.forename: Sandra
authors.initials: S
authors.lastname: Rozlan
authors.forename: Sandy
authors.initials: S
authors.lastname: Pelletier
authors.forename: Bernard
authors.initials: B
authors.lastname: Willems
authors.forename: Julie
authors.initials: J
authors.lastname: Bruneau
authors.forename: Jean-Daniel
authors.initials: JD
authors.lastname: Lelievre
authors.forename: Yves
authors.initials: Y
authors.lastname: Levy
authors.forename: Naglaa H
authors.initials: NH
authors.lastname: Shoukry
authors.forename: Rémi
authors.initials: R
authors.lastname: Cheynier
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D060085:Coinfection / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism; D005260:Female; D015658:HIV Infections / Q000276:immunology / Q000378:metabolism; D006526:Hepatitis C / Q000188:drug therapy* / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D007155:Immunologic Factors / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D016898:Interferon-alpha / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D015851:Interleukin-7 / Q000097:blood; D008231:Lymphopenia / Q000139:chemically induced; D008297:Male; D008875:Middle Aged; D016176:T-Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology; D013950:Thymus Gland / Q000187:drug effects / Q000276:immunology*
chemical_list: D000998:Antiviral Agents; D007155:Immunologic Factors; D016898:Interferon-alpha; D015851:Interleukin-7