Susan Kaech PhD

Associate Professor of Immunobiology; HHMI Early Career Scientist

Research Interests

Mechanisms of memory T cell development; Developmental Biology; Immunobiology; Immunology; Vaccine; Immunobiology; T-Cells; Vaccines; Adaptive immunity and immunological memory to viruses

Current Projects

Memory CD8 T cell differentiation

Memory CD4 T cell differentiation

Chronic viral infection

Research Summary

Memory T and B cells constitute our primary system of defense against reoccurring infectious disease, and therefore, the ability to form these cells is the ultimate goal of vaccination. My laboratory is interested in understanding how memory T cells are generated during infection and vaccination, and why in some circumstances, certain immunizations fail to induce long-term T cell immunity. Using several powerful model systems of infection in mice, we are beginning to elucidate the mechanisms involved in the development of protective and long-lived memory T cells. Our studies are primarily aimed at identifying the signals that regulate the differentiation of naïve CD8 T cells into effector cells and then into long-lived memory cells during the viral and bacterial infections of lymphocytic choriomeningitis virus (LCMV) and Listeria monocytogenes in mice.

Upon infection, naïve CD8 T cells encounter antigen and become activated, and this triggers the cells to rapidly divide and undergo massive clonal expansion. This activation also induces the cells to differentiate into effector T cells that can secrete cytokines and kill infected cells, and this leads to rapid clearance of the pathogen within a week's time. Following the resolution of infection, the effector cell population begins to contract and the majority of the cells die by apoptosis over the next 2-3 weeks. However, a minority of cells (~5-10%) escape this period of cell death and the cells that survive become the long-lived memory cell population. The number of memory cells remains remarkably constant over time and this is due to their ability to self-renewal by undergoing slow, periodic turnover that we refer to as 'homeostatic turnover', and these cells can protect against secondary infections.

A central question in memory T cell development is what is the decisive factor that determines which of the effector cells will survive and become long-lived memory cells and which will die during the contraction phase? Recently, we identified that the cytokine IL-7 plays an important role in this decision and that a subset of effector cells express higher levels of the IL-7 receptor (IL-7R). The heightened level of IL-7R predisposes this subset of effector cells to survive and preferentially develop into long-lived memory T cells. Thus, the selective expression of IL-7R on effector CD8 T cells identifies the memory cell precursors, and this now provides an excellent tool in which to further investigate the signals and mechanisms that regulate memory T cell development. Overall, our studies will help to improve the design of vaccines and immunotherapies aimed at fighting cancer and chronic infection.

Selected Publications

  • Cui W, Liu Y, Weinstein JS, Craft J & Kaech SM. An IL-21/IL-10/STAT3 pathway is critical for functional maturation of memory CD8+ T cells. Immunity 35:792-805 (2011). PMCID in progress.
  • Marshall HD, Chandele A, Jung YW, Meng H, Poholek AC, Parish IA, Rustishauser R, Cui W, Kleinstein SH, Craft J and Kaech SM. Differential Expression of Ly6C and T-bet Distinguish Effector and Memory Th1 CD4(+) Cell Properties during Viral Infection. Immunity 35:633-46 (2011). PMCID in process.
  • Joshi NS, Cui W, Dominguez CX, Chen JH, Hand TW and Kaech SM. Increased numbers of pre-existing memory CD8 T cells and decreased T-bet expression can restrain terminal differentiation of secondary effector and memory CD8 T cells. J Immunol 187(8):4068-76 (2011). PMCID in process.
  • Jung YW, Rutishauser R, Nikhil JS, Haberman AM and Kaech SM. Differential localization of effector and memory CD8 T cell subsets in lymphoid organs during acute viral infection. J Immunol 185:5315-25 (2010). PMCID in progress.
  • Hand TW, Jung YW, Cui W, Sefik E, Liu Y, Joshi NS, Chandele A and Kaech SM. Differential effects of STAT5 and P13K/AKT signaling on effector and memory CD8 T cell survival. PNAS 107:16601-6 (2010). PMCID: PMC2944719.
  • Poholek AC, Hansen K, Hernandez SG, Eto D, Chandele A, Dong, X, Odegard JM, Kaech SM, Dent AL, Crotty S and Craft J. Bcl6 regulation and TFH cell development. J Immunol 185:313-26 (2010). PMCID: PMC2891136.
  • Rutishauser RL, Martins GA, Kalachikov S, Chandele A, Parish IA, Jacob J, Calame K, Kaech SM. Blimp-1 is Required for the Terminal Differentiation of Virus-Specific Effector and Memory CD8 T cells. Immunity 31: 296-308 (2009).
  • Cui W, Joshi NS, Jiang A, Whitmire JK, Whitton JL, Kaech SM. Effects of Signal 3 during CD8 T cell priming: Bystander Production of IL-12 enhances effector T cell expansion but promotes terminal differentiation. Vaccine 27: 2177-87 (2009). PMID: 19201385.
  • Chandele A, Joshi NS, Zhu J, Paul WE, Leonard WJ, Kaech SM. Formation of IL-7Rahi and IL-7Ralo CD8 T Cells during Infection is Regulated by the Opposing Functions of GABPa and Gfi-1. J Immunol 8: 5309-19 (2008). PMID: 18390712.
  • Joshi NS, Cui W, Chandele A, Heung K-L, Urso D, Hagman J, Gapin L, Kaech SM. Inflammation Directs Memory Precursor and Short-Lived Effector CD8+ T Cell Fates via the Graded Expression of T-Bet Transcription Factor. Immunity 27: 281-295 (2007). PMID: 17723218.


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