Induction of polyfunctional human memory T cells by Wnt pathway activation (VAC3P.949)

Abstract

Polyfunctionality is a hallmark of protective immunity against pathogens and cancer. However, the molecular mechanisms governing the induction of polyfunctional T cells are not completely understood. We found that during antigen-driven expansion of human virus-specific T cells, Wnt pathway activation enhances the CD62L+, CD28+, and KLRG1- central memory T cell phenotype and promoted the generation of highly polyfunctional virus-specific T cells. Such effects are not only seen in influenza-specific responses but also in terminally differentiated CMV- and HIV-specific T cells. Mechanistically induction of polyfunctionality was independent of arresting antigen-specific cell expansion and is T cell-intrinsic. These findings provide the first evidence that Wnt pathway activation leads to polyfunctional antigen-specific memory human T cells responses and therefore have implications for treatment of chronic viral infections and cancer.