Molecular determinants of human T cell differentiation and host-pathogen interaction
Sundrud, Mark Scott
The differentiation of naive T helper (Th) cells into effector/memory subsets and their interaction with invading pathogens ultimately determines the outcome of infectious human diseases. The research detailed herein is aimed to delineate the transcriptional regulation of human Th cell differentiation and to further understand how these cells interact with microbial pathogens. Utilizing a lentiviral transduction system, we genetically modify primary human Th cells to further elucidate the roles of T-bet and GATA-3 during human Th cell differentiation. Furthermore, we describe how two important human pathogens, human immunodeficiency virus (HIV)-1 and Helicobacter pylori (H. pylori), usurp or perturb Th cell function, possibly contributing to their evasion of human immune responses. Our results lend novel insight into the regulation of human Th cell differentiation, function and interaction with pathogens. Moreover, this work has implications in the development of novel therapeutic strategies to manipulate Th cell function during infectious diseases or immunopathologies.