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

Marc Pellegrini, et al. Cell (2011) 144:601-613

Speaker: Pin-Hung Lin (林品宏)                                    Time: 13:10~14:00 May, 11, 2011

Commentator: Chun-Keung Yu, Ph.D. (余俊強 老師) Place: Room 601

Abstract

During chronic viral infection, immune system fails to clear virus and leads to uncontrolled viral turnover. The clone 13 strain of lymphocytic chorimeningitis virus (LCMV) establishes chronic infection in mice with a high dose of viral turnover and dysfunctional immune response. Thus clone 13 infection is a good model mimicking persistent viral infections, particularly like HBV, HCV, and HIV ¹. Previous studies have shown that interleukine-7 (IL-7), an essential factor for lymphocytes, maintains stable numbers of naïve and memory T cells ². However, the efficacy of IL-7 in viral clearance and in suppression of immune inhibitory network during chronic viral infection has not been fully reported. To address this issue, the authors treated clone13-infected mice with IL-7 starting at 8 days post-infection. After 3 weeks treatment, they found that IL-7 expanded viral-specific and non-LCMV-specific T cells through mechanisms of peripheral homeostasis and enhancing thymic output. IL-7 treatment enhanced viral clearance, down-regulated PD-1 on effector T cells, and limited the numbers of T regulatory cells. They further found that IL-7 promoted the secretion of proinflammtory cytokines during clone 13 infection by suppressing Socs3. Furthermore, IL-7 treatment also expanded Th17 cells, which produced high levels of IL-17, IL-6, and IL-22 to protect hepatocytes from T cell-mediated liver pathology. Collectively, these results suggest that IL-7 has a potential role in treatment of chronic viral diseases.

References:

1.      Elizabeth B. Wilson, David G. Brooks .Translating insights from persistent LCMV infection into anti-HIV immunity. Immunologic Research (2010) 48:3-13

2.      Christina Kittipatarin, Annette R. Khaled. Interlinking interleukin-7. Cytokine (2007) 39:75-83