Development of a model system to study the role of thymic nurse cells in T cell development.
Item
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Title
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Development of a model system to study the role of thymic nurse cells in T cell development.
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Identifier
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AAI9304719
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identifier
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9304719
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Creator
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Pezzano, Mark Thomas.
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Contributor
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Adviser: Jerry Guyden
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Date
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1992
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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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Health Sciences, Immunology | Biology, Cell | Biology, Molecular
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Abstract
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Thymic nurse cells (TNC) are large thymic epithelial cells which contain 20-200 developing thymocytes within specialized vacuoles in their cytoplasm. The purpose of the uptake of thymocytes by TNCs is unknown. However, TNCs have the capacity to present self-antigens, which implies that they may serve a function in the process of thymic education. We report here the development of two cell lines, which together constitute a model system with which to study the role of TNCs in T cell development. The first cell line, called TBL-1, expresses some characteristics of early T cells. TBL-1 occurred spontaneously from mouse thymus organ cultures derived from C57BL/6 mice. After cloning, the only T cell surface marker expressed by TBL-1 is Lyt-1. Analysis of the T cell antigen receptor (TCR) genes shows that they rearrange the {dollar}\alpha{dollar} and {dollar}\gamma{dollar} genes and express full length {dollar}\alpha{dollar} and {dollar}\gamma{dollar} mRNA transcripts, thus the {dollar}\delta{dollar} gene is completely deleted. An immature 1.0 Kb {dollar}\beta{dollar} mRNA is transcribed from an unrearranged {dollar}\beta{dollar} gene. TBLs cannot produce either an {dollar}\alpha{dollar}/{dollar}\beta{dollar} or {dollar}\gamma{dollar}/{dollar}\delta{dollar} TCR. TBLs thus have little potential to mature along any known T cell developmental pathway. They do, however, specifically bind to both freshly isolated thymic nurse cells and the second cell line in our model system (MP5). The SVT-MP5 cell line is an SV40 transformed thymic nurse cell line derived from C57BL/6 mice. This cell line has been characterized using a panel of antibodies against markers used to identify TNCs. MP5 was shown to express A2B5, class I and class II MHC, and cytokeratin. In addition they were shown to bind and internalize both fresh thymocytes and the TBL-1 cell line. Internalization of thymocytes is unique to SV40 infected TNCs and TNCs within the thymus. The MP5 and TBL-1 cell lines together represent a model system with which we can determine the proteins involved in the internalization process as well as the role of TNC internalization in T cell development.
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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.
