Modulating cytokine expression by T cells to protect the mucosa from chronic viral infections.

Inducing effective antiviral immunity at mucosal surfaces will be critical to inhibit the transmission and persistence of numerous pathogenic viruses. Using the murine cytomegalovirus (MCMV) model, I discovered that chronic mucosal infection induces expression of the suppressive cytokine IL-10 by CD4 T cells, which subsequently antagonises antiviral immunity. Aim 1 of this proposal will elucidate factors driving the development of IL-10+ T cells during infection. Aim 2 will characterise the gene expression profile of IL-10+ T cells and test whether cell-surface molecules preferentially expressed by these suppressive cells promotes their expansion and function. The IL-10-related cytokine IL-22 protects barrier surfaces from bacteria. I have discovered that IL-22 affords protection from mucosal MCMV infection. Aim 3 will elucidate how IL-22 exerts antiviral activity in mucosal and non-mucosal tissue, and Aim 4 seeks to identify how to elicit IL-22 production by T cells and test whether t his enhances T cell mediated protection from mucosal MCMV infection. These experiments will uncover novel immune mechanisms that protect mucosal tissue from herpesvirus infections and, in combination with Aims 1 and 2, will identify approaches to improving anti-viral T cell responses in order to ensure protection of mucosal tissue from chronic viral infections.