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.