title: Immunotherapeutic effects of IL-7 during a chronic viral infection in mice.
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.
authors: Department of Pathobiological Sciences, University of Wisconsin-Madison, Madison, WI, USA.
authors: Som G
authors: SG
authors: Nanjappa
authors: Eui Ho
authors: EH
authors: Kim
authors: M
authors: M
authors: Suresh
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D002469:Cell Separation; D002908:Chronic Disease; D005434:Flow Cytometry; D007155:Immunologic Factors / Q000627:therapeutic use*; D015851:Interleukin-7 / Q000627:therapeutic use*; D008216:Lymphocytic Choriomeningitis / Q000188:drug therapy* / Q000276:immunology / Q000821:virology; D051379:Mice; D008810:Mice, Inbred C57BL
chemical_list: D007155:Immunologic Factors; D015851:Interleukin-7