The role of thymic nurse cells in T cell development.
Item
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Title
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The role of thymic nurse cells in T cell development.
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Identifier
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AAI9959215
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identifier
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9959215
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Creator
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Philp, Deborah D.
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Contributor
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Adviser: Jerry C. Guyden
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Date
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2000
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Language
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English
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Publisher
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City University of New York.
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Subject
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Biology, Cell | Biology, Molecular
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Abstract
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Thymic nurse cells (TNCs) are stromal epithelial cells located in the thymic cortex. A single TNC may contain as many as 200 thymocytes in specialized intra-thymic vacuoles. Very little is known about the process of thymocyte internalization or the phenotypic and molecular changes occurring in developing thymocytes as a function of their interaction with TNCs. The thymocyte-TNC interaction has been difficult to study because TNCs can only be identified and isolated after their interaction with thymocytes in the thymus. Freshly isolated TNCs lack thymocyte internalization capabilities in vitro .;The goal of this study was to determine the role played by TNCs in T cell development. The immortalization and development of TNC lines, using SV40 virus (strain PH911) and a temperature sensitive mutant of the SV40 virus (tsA58), provided an ideal model system for studying the function of TNCs in the thymus and their role in T cell development. Previous studies have described functions that are unique to TNCs and have shown that freshly isolated TNCs and immortalized TNC lines possess similar qualities. Electron microscopy and long-term video microscopy were used to show that the thymocyte-TNC interaction occurred via membrane ruffling and is a selective process. This interactive population displayed a phenotype identical to that of thymocytes prior to MHC restriction; TCRloCD4+CD8+CD69 -. A select subpopulation of these thymocytes were rescued from apoptosis as a function of this interaction. The rescued population displayed phenotypic changes characteristic of positive selection and maturation. The resulting thymocyte population displayed a phenotype that is identical to cells that have survived thymic education. The costimulatory effects of the lymphokine IL-1beta were required for maturation of the rescued thymocyte population. Blocking studies against MHC class I and class II showed that the MHC-TCR interaction between these two cell types was also required for thymocyte rescue. The non-interactive thymocyte population underwent apoptosis. A population of cells that were not released from the TNCs underwent apoptosis within the TNC's specialized vacuoles. Comparable events were occurring in vivo suggesting that TNCs may be involved in selection and play a crucial role in thymic education.
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Type
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dissertation
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Source
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PQT Legacy CUNY.xlsx
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degree
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Ph.D.
