Immunotherapeutics effects of IL-7 during a chronic viral infection (44.13)

Abstract

Abstract Viral persistence in chronic infections is associated with ineffective T cell responses. Here, we evaluated the therapeutic use of IL-7 to enhance T cell responses during a chronic infection with lymphocytic choriomeningitis virus (LCMV). Mice infected with Clone 13 strain of LCMV were treated with IL-7 at various intervals spanning the first 30 days after infection. Our studies show that the ability of IL-7 to enhance T cell responses to a chronic viral infection is constrained by high viral load. Early in the infection (days 0-15 PI), when the viral load is very high, IL-7 administration induced minimal enhancement of T cell responses to LCMV. However, with reducing viral load (after day 15 PI), IL-7 augmented virus-specific T cell responses, albeit temporarily. An extended duration of IL-7 treatment after the initial phase of T cell expansion (days 8-30 PI), markedly enhanced the number of virus-specific CD8 T cells. Moreover, extended IL-7 therapy altered the cell surface phenotype, and augmented the cytokine-producing ability of LCMV-specific T cells. Surprisingly, despite the augmentation of virus-specific T cell responses, IL-7 therapy had a modest effect on circulating viral load in chronically infected mice. In summary, these findings suggested that IL-7 administration could be used as an adjunct to anti-viral immunotherapy to bolster T cell responses to chronic viral infections. This work was supported by PHS grant AI68841 to M. Suresh.