Interleukin-7 (IL-7): immune function, involvement in the pathogenesis of HIV infection and therapeutic potential.
Interleukin 7 (IL-7), which is constitutively produced particularly by stromal cells from the bone marrow and thymus, plays a crucial role in T cell homeostasis. This cytokine is implicated in thymopoiesis since it sustains thymocyte proliferation and survival. It regulates peripheral naive T cell survival by modulating the expression of the anti-apoptotic molecule Bcl-2, and sustains peripheral T cell expansion in response to antigenic stimulation. Infection by the human immunodeficiency virus (HIV) leads to severe T lymphopenia and general immune dysfunction. Increased IL-7 plasma levels are generally observed in HIV-infected patients. The existence of an inverse correlation between IL-7 plasma levels and the CD4+ T cell count suggests that a direct feedback mechanism is working to restore peripheral T cell counts in lymphopenic patients. Here, IL-7 plasma levels are a good predictive marker of CD4+ T cell restoration during therapy. Combinations of antiretroviral treatments considerably slow disease progression. They drastically decrease the viral load and, in most patients, significantly increase peripheral CD4+ T cell counts. However, despite their usual ability to reduce viral replication, such treatments often fail to reverse lymphopenia and do not restore specific antiviral immune responses. IL-7, based therapy, combined with efficient antiretroviral treatment, may be beneficial to HIV-infected patients by promoting thymic output, sustaining naive T cell counts and increasing memory T cell activation.
Beq
Stéphanie
S
Unité d'Immunogénétique Cellulaire, Département de Médecine Moléculaire, Institut Pasteur, 25 rue du Dr Roux, 75724 Paris Cedex 15, France.
Delfraissy
Jean-François
JF
Theze
Jacques
J
D023241:Antiretroviral Therapy, Highly Active; D001854:Bone Marrow Cells / Q000166:cytology / Q000276:immunology; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D006678:HIV / Q000502:physiology*; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology; D006801:Humans; D015851:Interleukin-7 / Q000276:immunology* / Q000627:therapeutic use; D038041:Lymphopoiesis / Q000276:immunology*; D017154:Stromal Cells / Q000276:immunology; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology; D019562:Viral Load; D014779:Virus Replication / Q000276:immunology*
D015851:Interleukin-7