Author/Authors :
Marc Pellegrini، نويسنده , , Thomas Calzascia، نويسنده , , Jesse G. Toe، نويسنده , , Simon P. Preston، نويسنده , , Amy E. Lin، نويسنده , , Alisha R. Elford، نويسنده , , Arda Shahinian، نويسنده , , Philipp A. Lang، نويسنده , , Karl S. Lang، نويسنده , , Michel Morre، نويسنده , , Brigitte Assouline، نويسنده , , Katharina Lahl، نويسنده , , Tim Sparwasser، نويسنده , , Thomas F. Tedder، نويسنده , , Ji-Hye Paik، نويسنده , , Ronald A. DePinho، نويسنده , , Sameh Basta، نويسنده , , Pamela S. Ohashi، نويسنده , , Tak W. Mak، نويسنده ,
Abstract :
Understanding the factors that impede immune responses to persistent viruses is essential in designing therapies for HIV infection. Mice infected with LCMV clone-13 have persistent high-level viremia and a dysfunctional immune response. Interleukin-7, a cytokine that is critical for immune development and homeostasis, was used here to promote immunity toward clone-13, enabling elucidation of the inhibitory pathways underlying impaired antiviral immune response. Mechanistically, IL-7 downregulated a critical repressor of cytokine signaling, Socs3, resulting in amplified cytokine production, increased T cell effector function and numbers, and viral clearance. IL-7 enhanced thymic output to expand the naive T cell pool, including T cells that were not LCMV specific. Additionally, IL-7 promoted production of cytoprotective IL-22 that abrogated liver pathology. The IL-7-mediated effects were dependent on endogenous IL-6. These attributes of IL-7 have profound implications for its use as a therapeutic in the treatment of chronic viral diseases.
