Immunotherapeutic effects of IL-7 during a chronic viral infection in mice

SG Nanjappa, EH Kim, M Suresh - Blood, The Journal of the …, 2011 - ashpublications.org
Blood, The Journal of the American Society of Hematology, 2011ashpublications.org
Viral persistence during chronic viral infections is associated with a progressive loss of T-cell
effector function called functional exhaustion. There is therefore a need to develop
immunotherapies to remediate the functional deficits of T cells during these infections. We
investigated the immunotherapeutic effects of IL-7 during chronic lymphocytic
choriomeningitis virus infection in mice. Our results showed that the effects of IL-7 on T cells
depend on the viral load, timing, and duration of treatment during the course of the infection …
Abstract
Viral persistence during chronic viral infections is associated with a progressive loss of T-cell effector function called functional exhaustion. There is therefore a need to develop immunotherapies to remediate the functional deficits of T cells during these infections. We investigated the immunotherapeutic effects of IL-7 during chronic lymphocytic choriomeningitis virus infection in mice. Our results showed that the effects of IL-7 on T cells depend on the viral load, timing, and duration of treatment during the course of the infection. We document that the effectiveness of IL-7 was constrained by high viral load early in the infection, but treatment for at least 3 weeks during declining viral titers mitigated the programmed contraction of CD8 T cells, markedly enhanced the number of high-quality polyfunctional virus-specific CD8 T cells with a nonexhausted phenotype, and accelerated viral control. Mechanistically, the enhancement of CD8 T-cell responses by IL-7 was associated with increased proliferation and induction of Bcl-2, but not with altered levels of PD-1 or Cbl-b. In summary, our results strongly suggest that IL-7 therapy is a potential strategy to bolster the quality and quantity of T-cell responses in patients with chronic viral infections.
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