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IL-7 Engages Multiple Mechanisms to Overcome Chronic Viral Infection and Limit Organ Pathology


Pellegrini, M; Calzascia, T; Toe, JG; Preston, SP; Lin, AE; Elford, AR; Shahinian, A; Lang, PA; Lang, KS; Morre, M; Assouline, B; Lahl, K; Sparwasser, T; Tedder, TF; Paik, JH; DePinho, RA; Basta, S; Ohashi, PS; Mak, TW
2011-02-18
CELL
Journal Article
144
4
601-613
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 down-regulated 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.
CELL PRESS
CD4(+) T-CELLS; IN-VIVO; LYMPHOID-TISSUE; HOST-DEFENSE; INTERLEUKIN-22; ACTIVATION; EXPANSION; INFLAMMATION; PERSISTENCE; HEPATOCYTES
10.1016/j.cell.2011.01.011
Refer to copyright notice on published article.

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Creation Date 2011-02-18 12:00:00