Department of Immunology and Microbial Science
Head, Flow Cytometry Core
Like all cells of hematopoietic origin, new T lymphocytes must be generated throughout life, a task that is the primary function of the thymus. Unlike other tissues that undergo steady-state differentiation, however, the thymus contains no self-renewing progenitor cells. Instead, new progenitors are specifically recruited from a pool of multi-potent progenitors that circulate within the blood. Once inside the thymus, these progenitors undergo a series of cell divisions to generate a large pool of T-lineage restricted cells that undergo selection based on the specificity of their antigen receptors, and are ultimately exported to the peripheral immune system. Our laboratory focuses on the early aspects of the intrathymic differentiation process, particularly on those aspects that relate to thymic homing, proliferative expansion, and T lineage commitment. In recent years, we have shown that different phases of these processes take place in specific tissue regions within the thymus, indicating the presence of different signaling microenvironments in the thymus, and obligating the existence of a system for moving progenitors between them.
Currently, we are focusing on the following goals:
Ph.D., University of Nebraska Medical Center, 1988
Griffith AV, Fallahi M, Venables T, and Petrie HT. 2012. Persistent degenerative changes in thymic organ function revealed by an inducible model of organ regrowth. Aging Cell: in press.
Shi J, Fallahi M, Luo JL, and Petrie HT. 2011. Non-overlapping functions for Notch1 and Notch3 during murine steady-state thymic lymphopoiesis. Blood 118:2511-2519.
Griffith AV, Fallahi M, Nakase H, Gosink M, Young B, and Petrie HT. 2009. Spatial mapping of thymic stromal microenvironments reveals unique features influencing T lymphoid differentiation. Immunity: 31:999-1009.
Umland O, Mwangi WN, Anderson B, Walker J, and Petrie HT. 2007. The blood contains multiple distinct progenitor populations with clonogenic B and T lineage potential. J Immunol 178:4147-4152.
Petrie HT and Zúñiga-Pflücker JC. 2007. Zoned out: functional mapping of stromal signaling microenvironments in the thymus. Ann Rev Immunol 25:6649-6679.
Porritt HE, Rumfelt LL, Tabrizifard S, Schmitt TM, Zúñiga-Pflücker JC, Petrie HT. 2004. Heterogeneity among DN1 prothymocytes reveals multiple progenitors with different capacities to generate T cell and non-T cell lineages. Immunity 20:735-745.