<p>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.</p>
Emory University School of Medicine
University of Washington
University of Utah
- Baessler A, Fuchs B, Perkins B, Richens AW, Novis CL, Harrison-Chau M, Sircy LM, Thiede KA, Hale JS (2023). Tet2 deletion in CD4+ T cells disrupts Th1 lineage commitment in memory cells and enhances T follicular helper cell recall responses to viral rechallenge. Proc Natl Acad Sci U S A, 120(36), e2218324120.
- Galloway DR, Nguyen NX, Li J, Houston N, Gregersen G, Williamson ED, Falkenberg FW, Herron JN, Hale JS (2022). The magnitude of the germinal center B cell and T follicular helper cell response predicts long-lasting antibody titers to plague vaccination. Front Immunol, 13, 1017385.
- Jensen O, Trivedi S, Li K, Aub J, Hale JS, Ryan ET, Leung DT (2022). Use of a MAIT-Activating Ligand, 5-OP-RU, as a Mucosal Adjuvant in a Murine Model of Vibrio cholerae O1 Vaccination. Pathog Immun, 7(1), 122-144.
- Baessler A, Novis CL, Shen Z, Perovanovic J, Wadsworth M, Thiede KA, Sircy LM, Harrison-Chau M, Nguyen NX, Varley KE, Tantin D, Hale JS (2022). Tet2 coordinates with Foxo1 and Runx1 to balance T follicular helper cell and T helper 1 cell differentiation. Sci Adv, 8(24), eabm4982.
- Jensen O, Trivedi S, Meier JD, Fairfax KC, Hale JS, Leung DT (2022). A subset of follicular helper-like MAIT cells can provide B cell help and support antibody production in the mucosa. Sci Immunol, 7(67), eabe8931.
- Trivedi S, Labuz D, Anderson CP, Araujo CV, Blair A, Middleton EA, Jensen O, Tran A, Mulvey MA, Campbell RA, Hale JS, Rondina MT, Leung DT (2020). Mucosal-associated invariant T (MAIT) cells mediate protective host responses in sepsis. Elife, 9.
- Baessler A, Hale JS (2019). Recurrent Tonsillitis Tfh Cells Acquire a Killer Identity. Trends Immunol, 40(5), 377-379.
- Olatunde AC, Hale JS, Lamb TJ (2021). Cytokine-skewed Tfh cells: functional consequences for B cell help. [Review]. Trends Immunol, 42(6), 536-550.