Regulation of mucosal memory CD8 T cells by Thymic Stromal Lymphopoietin

University Of Georgia, Athens GA

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Abstract

DESCRIPTION (provided by applicant): Thymic Stromal Lymphopoietin (TSLP) is a recently described cytokine which shares a receptor component (IL-7Ra) and significant biological redundancy with Interleukin-7. TSLP is predominately expressed by mucosal epithelial cells, which positions TSLP to play a role in orchestrating immune responses during infection with oral pathogens, including L. monocytogenes. Receptors for TSLP are not only expressed by CD8 T cells but also by dendritic cells which actively participate in shaping the generation of CD8 T cell memory. The goal of this proposal is to understand how TSLP both directly and indirectly affects the formation and maintenance of CD8 T cell memory. In Aim 1 we will study the kinetics of TSLP expression during oral L. monocytogenes infection and examine TSLP receptor expression on anti-bacterial CD8 T cells. We will use transgenic animals to modulate either TSLP or TSLP receptor expression to determine how the cytokine directly interacts with and impacts the fate of mucosal memory CD8 T cells. In Aim 2 we will use both in vitro culture systems and genetically modified animals to determine how populations of TSLP-conditioned DCs affect CD8 T cell priming, memory development, and homeostasis during enteric infection. Together, these studies will provide a global view of how TSLP regulates multiple lineages of cells which play active roles in CD8 T cell biology and will further our understanding of mucosal memory CD8 T cell development. This in turn will help in designing novel therapeutic interventions and vaccines, particularly those aimed at boosting immune responses at mucosal surfaces.