Assistant Professor of Pathology
B.A. University of Utah
Ph.D. University of Washington
Scott Hale's Lab Page
Scott Hale's PubMed Literature Search
Molecular Biology Program
T cell responses to viral infection and immunization; Epigenetic programing of helper T cell differentiation
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.
Major projects in the lab include:
- Investigate how different types of infections and protein immunizations affect the lineage commitment versus plasticity and function of Tfh and non-Tfh memory cells.
- Determine whether Tfh and Th1 memory cells maintain their lineage stability and functions following multiple infections/ boosts, or during persistent viral infection.
- Gene expression programming mediated by changes in DNA methylation that regulate the differentiation and maintenance of memory T helper cell subsets.
- The role of the transcription factor Tbet in Tfh and Th1 cell function during acute and chronic viral infection.
Arthur CM, Patel SR, Smith NH, Bennett A, Kamili NA, Mener A, Gerner-Smidt C, Sullivan HC, Hale JS, Wieland A, Youngblood B, Zimring JC, Hendrickson JE, Stowell SR (2017). Antigen Density Dictates Immune Responsiveness following Red Blood Cell Transfusion. J Immunol, 198(7): 2671-2680.
Ye L, Lee J, Xu L, Mohammed AU, Li W, Hale JS, Tan WG, Wu T, Davis CW, Ahmed R, Araki K (2017). mTOR Promotes Antiviral Humoral Immunity by Differentially Regulating CD4 Helper T Cell and B Cell Responses.LID - e01653-16 [pii]LID - 10.1128/JVI.01653-16 [doi]. J Virol: 91(4).
Im SJ, Hashimoto M, Gerner MY, Lee J, Kissick HT, Burger MC, Shan Q, Hale JS, Lee J, Nasti TH, Sharpe AH, Freeman GJ, Germain RN, Nakaya HI, Xue HH, Ahmed R (2016). Defining CD8+ T cells that provide the proliferative burst after PD-1 therapy. Nature, 537(7620): 417-421.
Wu T, Wieland A, Lee J, Hale JS, Han JH, Xu X, Ahmed R (2015). Cutting Edge: miR-17-92 Is Required for Both CD4 Th1 and T Follicular Helper Cell Responses during Viral Infection. J Immunol, 195(6): 2515-9.
- Hale JS, Youngblood B, Latner DR, Mohammed AU, Ye L, Akondy RS, Wu T, Iyer SS, and Ahmed R (2013). Distinct memory CD4+ T cells with commitment to T follicular helper- and T helper 1- cell lineages are generated after acute viral infection. Immunity. 38:805-817.
- Iyer SS, Latner DR, Zilliox MJ, McCausland M, Akondy RS, Macmaster-Penaloza P, Hale JS, Ye L, Mohammed AU, Yamaguchi T, Sakaguchi S, Amara RR, Ahmed R (2013). Identification of novel markers for mouse CD4+ T follicular helper cells. J. Immunol. 43:3219-3232.
- O’Leary MN, Schreiber KH, Zhang Y, Duc AC, Rao S, Hale JS, Academia EC, Shah SR, Morton JF, Holstein CA, Martin DB, Kaeberlein M, Ladiges WC, Fink PJ, Mackay VL, Wiest DL, Kennedy BK (2013). The ribosomal protein rpl22 controls ribosome composition by directly repressing expression of its own paralog, rpl22l1. PLoS Genet. Aug;9(8):e1003708.
- Wu T, Wieland A, Araki K, Davis CW, Ye L, Hale JS, and Ahmed R (2012). Temporal expression of microRNA cluster miR-17-92 regulates effector and memory CD8+ T-cell differentiation. Natl. Acad. Sci USA. 109:9965-9970.
- Hale JS** and Ahmed R (2015). Memory T follicular helper CD4 T cells. Immunol. 6: Article 16:1-9. (**corresponding author).
- Youngblood B, Hale JS, and Ahmed R (2015). Memory CD8 T cell transcriptional plasticity. F1000Prime Rep. 7:38.
- Youngblood B*, Hale JS*, and Ahmed R (2013). T-cell memory differentiation: insights from transcriptional signatures and epigenetics. Immunology. 139:277-284. (*authors contributed equally).
- Youngblood B, Hale JS, and Akondy R (2013). Using epigenetics to define vaccine-induced memory T cells. Opin. Virol. 3:371-376.