Altered thymic function during interferon therapy in HCV-infected patients

PLoS One. 2012;7(4):e34326. doi: 10.1371/journal.pone.0034326. Epub 2012 Apr 16.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antiviral Agents / adverse effects
  • Antiviral Agents / pharmacology
  • Antiviral Agents / therapeutic use*
  • Coinfection / drug therapy
  • Coinfection / immunology
  • Coinfection / metabolism
  • Female
  • HIV Infections / immunology
  • HIV Infections / metabolism
  • Hepatitis C / drug therapy*
  • Hepatitis C / immunology*
  • Hepatitis C / metabolism
  • Humans
  • Immunologic Factors / adverse effects
  • Immunologic Factors / pharmacology
  • Immunologic Factors / therapeutic use*
  • Interferon-alpha / adverse effects
  • Interferon-alpha / pharmacology
  • Interferon-alpha / therapeutic use*
  • Interleukin-7 / blood
  • Lymphopenia / chemically induced
  • Male
  • Middle Aged
  • T-Lymphocyte Subsets / drug effects
  • T-Lymphocyte Subsets / immunology
  • Thymus Gland / drug effects
  • Thymus Gland / immunology*


  • Antiviral Agents
  • Immunologic Factors
  • Interferon-alpha
  • Interleukin-7