Journal
BLOOD
Volume 117, Issue 19, Pages 5123-5132Publisher
AMER SOC HEMATOLOGY
DOI: 10.1182/blood-2010-12-323154
Keywords
-
Categories
Funding
- Public Health Service [AI48785, AI59804, AI68841]
Ask authors/readers for more resources
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. (Blood. 2011; 117(19): 5123-5132)
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available