My lab is primarily interested in T cell development in the thymus. We study how selection processes shape the T cell repertoire to achieve a highly effective and self-tolerant adaptive immune system.
Primarily interested in T cell development in the thymus. We study how selection processes shape the T cell repertoire to achieve a highly effective and self-tolerant adaptive immune system. Current research is focused on these four topics: Positive selection: This is a crucial stage in T cell development, where MHC restricted progenitors are selected from a random pool. We are systematically studying the gene changes that occur in the T cell progenitor during positive selection and how they support the multiple facets of this event (e.g. survival, migration, allelic exclusion, etc). We are also exploring how cortical epithelial cells support the process of positive selection Negative selection : One of the ways the immune system copes with self-reactive T cells is to eliminate them from the repertoire. We developed a highly physiologic in vivo mouse model to study the specific antigen-presenting cell types involved and the timing and anatomic location of negative selection. We are also exploring why some self-reactive cells undergo apoptosis, but others are selected to become regulatory T cells or NKT cells. Thymic Emigration : The lab is currently interested in the final stages of maturation that occur prior to migration of the progenitor from the thymus to the periphery. We seek to understand how the functional competence of the cell is eventually switched from apoptosis to proliferation, and the signals, molecular factors, and anatomic structures involved in emigration itself. Recent studies have focused heavily on the transcription factor KLF2. The Human T cell repertoire : We have a unique collaboration with a clinical virology group to study immune responses in humans that are at high risk for natural infection with a gamma herpesvirus (Epstein Barr Virus or EBV). In addition to documenting the precise changes that occur during the innate and adaptive immune response to this virus, we are exploring how the pre-immune T cell repertoire in such individuals is predisposed to make a pathologic response to this virus (infectious mononucleosis).
Zhang, Z., Salgado, O. C., Liu, B., Moazzami, Z., Hogquist, K. A., Farrar, M. A. & Ruan, H. B. An OGT-STAT5 Axis in Regulatory T Cells Controls Energy and Iron Metabolism. Frontiers in immunology; 2022, 13, 874863.
Peng, C., Huggins, M. A., Wanhainen, K. M., Knutson, T. P., Lu, H., Georgiev, H., Mittelsteadt, K. L., Jarjour, N., Wang, H., Hogquist, K. A., Campbell, D. J., Borges da Silva, H. & Jameson, S. C., Engagement of the costimulatory molecule ICOS in tissues promotes establishment of CD8+ tissue-resident memory T cells. Immunity; Jan 11 2022; 55, 1, p. 98-114.e5
Georgiev, H., Peng, C., Huggins, M.A., Jameson S. C., Hogquist, K.A. Classical MHC expression by DP thymocytes impairs the selection of non-classical MHC restricted innate-like T cells. Nat Commun 12, 2308 (2021). https://doi.org/10.1038/s41467-021-22589-z
Ruscher R, Thera Lee S, Salgado OC, Breed ER, Osum SH, and Hogquist KA. Intestinal CD8?? IELs derived from two distinct thymic precursors have staggered ontogeny. J Exp Med 3 August 2020; 217 (8): e20192336. doi: https://doi.org/10.1084/jem.20192336
Wang H, Breed ER, Lee YJ, Qian LJ, Jameson SC, Hogquist KA. Myeloid cells activate iNKT cells to produce IL-4 in the thymic medulla. Proc Natl Acad Sci U S A. 2019 Oct 29;116(44):22262-22268. doi: 10.1073/pnas.1910412116. Epub 2019 Oct 14.
Borges da Silva H, Beura LK, Wang H, Hanse EA, Gore R, Scott MC, Walsh DA, Block KE, Fonseca R, Yan Y, Hippen KL, Blazar BR, Masopust D, Kelekar A, Vulchanova L, Hogquist KA, Jameson SC. The purinergic receptor P2RX7 directs metabolic fitness of long-lived memory CD8+ T cells. Nature. 2018 Jul;559(7713):264-268. doi: 10.1038/s41586-018-0282-0. Epub 2018 Jul 4.
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