The overall goal of this project is to characterize basic immunologic properties of murine intestinal intraepithelial lymphocytes (IEL), and to study the role of the IEL in intestinal immunity and immunopathology. These studies are a continuation of work initiated under a New Investigator Award to John R. Klein, Ph.D.
The first aim of this project is to phenotypically define component IEL subset populations using lymphocyte-specific antigenic markers. Phenotypically-defined IEL subsets will be correlated with functional activities. Emphasis will be placed on characterizing IEL which express unique properties whose functional role has not been fully established. Among these are the CT+ and the Thy-1-, Lyt-2+ IEL subsets. Questions of IEL ontogeny will be addressed using antibodies to murine T cell receptor (TCR) allotypic markers, and by northern blot analyses to identify IEL populations which express, and presumably utilize, TCR molecules. TCR gene rearrangements in IEL will be determined by southern blot analyses to provide insight into the ontogeny, i.e., the thymus origin, of those cells.
The second aim of this project is the use IEL-derived CTL clones previously isolated in this laboratory in studies of IEL specificity and antigen recognition (CTL vs NK). Additionally, IEL CTL clones specific for enteric pathogens will be isolated and used in the following experiments.
A third aim of this project is to probe mechanisms of IEL- mediated immunity and immunopathology using virus-specific CTL clones (and uncloned isolates). The involvement of IEL during, and subsequent to virus infection will be studied as a potential in vivo model of immunologically-mediated human intestinal disorders.
A fourth aim of this project is the use IEL-specific monoclonal antibodies isolated in this laboratory in studies of IEL ontogeny and function, and/or as a method for improving IEL isolation techniques.
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