J. Scott Hale, PhD

Research Statement

My laboratory studies T cells and their role in the generation of immunological memory in response to viral infection and immunization. Upon activation, naïve CD4+ T cells proliferate and differentiate to become distinct types of T helper cell subsets that have specialized effector functions that are tailored to protect the host against the specific type of invading pathogen. During acute viral infection, newly activated CD4+ T cells differentiate into two functionally distinct T helper cell subsets: 1) Th1 cells that secrete IFNγ and contribute to cell-mediated immunity; and 2) Follicular helper T cells (Tfh) that migrate to B cell follicles and provide critical help to germinal center B cells and the generation of long-lived antibody responses. Following viral clearance, these subsets of T helper cells can become long-lived memory T cells that are poised to rapidly respond to reinfection by recalling their effector functions. Our studies focus on understanding the signals and mechanisms that promote the differentiation of these functionally unique subsets of effector and memory T cells and determine how these cells can be utilized to improve protective immune responses. We utilize various models of infection and vaccination in mice to study the basic mechanisms of T cell differentiation and function. We take advantage of mouse knockout and conditional knockout models to understand how transcription factors and epigenetic regulators modulate the gene expression programing and function of pathogen-specific effector and memory T cell subsets. Understanding how T cells acquire and maintain their specialized functions will provide important insights that can be used to improve prime and boost vaccination strategies to generate long-lived protective immunity against infectious diseases.