Differential thymocyte motility and microenvironmental localization during normal and neoplastic T cell development (111.55)

Abstract

Abstract As thymocytes develop, they modulate expression of receptors, such as chemokine receptors, that promote migration into distinct thymic microenvironments. Within these thymic regions, developing thymocytes have the opportunity to interact with unique stromal cells that provide survival, selection, and/or differentiation signals. Thymocyte: stromal interactions are essential for proper thymocyte development, implicating the molecules involved in regulating intrathymic migration as key regulators of T cell development. Previously, we have used 2-photon microscopy to study real-time migration of thymocytes within live thymic slices. These studies revealed that immature thymocyte progenitors were restricted to the cortex while only post-positive selection thymocytes were able to enter the medulla. The ability to migrate within cortex versus medulla was regulated by multiple mechanisms, including G-protein coupled receptor mediated chemotaxis and substrate accessibility. We hypothesize that the molecular cues that mediate normal intrathymic migration may be disrupted during thymic lymphomagenesis, contributing to the initiation and/or progression of disease. Consistent with this hypothesis, we find that the thymic microenvironment is disorganized in a murine model of thymic lymphoma. Furthermore, using 2-photon microscopy, we find that migration of lymphoma cells within thymic tissue is abnormal, suggesting that aberrant thymocyte: stromal interactions may contribute to disease.