The Thymus and T Cell Differentiation
{'Code': '08070600', 'Directorate': {'Abbreviation': 'BIO', 'LongName': 'Direct For Biological Sciences'}, 'Division': {'Abbreviation': 'MCB', 'LongName': 'Div Of Molecular and Cellular Bioscience'}}
{'SignBlockName': 'Maryanna P. Henkart', 'PO_EMAI': None, 'PO_PHON': None}
The role of the thymus in the positive and negative selection                   (tolerance) of T lymphocytes is currently a subject of intense                  interest in the immunological community.  Many of the models used               to study this problem entail considerable perturbation of normal                physiology.  Xenopus offers an opportunity to examine this                      selection by the production of embryonic head/body chimeras in                  which the thymus anlagen and the precursors of all hematopoietic                cells are transplanted across major histocompatibility (MHC)-                   disparate barriers.  The work to date suggests that the thymus                  epithelium itself positively selects T cells that can recognize                 antigen in association with the thymus's MHC, but cannot make                   tolerant cells which are reactive with the thymus's MHC.  T cells               are present within the chimeras that are reactive in the mixed                  leukocyte reaction (MLR) with stimulator cells bearing the                      thymus's MHC-type, but these cells do not reject the anterior                   region of the chimera or subsequent skin grafts from normal                     animals with the MHC-type of the thymus (split tolerance).  The                 goal of this work is to test certain models pertaining to                       positive and negative selection.  Specifically, the MLR against                 the thymus's MHC will be further studied to determine which MHC                 antigens, and possibly which form of the antigens, are recognized               by the anti-thymus T cells.  Several in vivo protocols involving                the transfer of lymphocytes from chimeras into normal animals,                  primed cells from normal frogs into chimeras, and the examination               of an "autoimmune" antibody response to the thymus's class I                    molecules, will be performed in the hope of determining whether                 the in vitro reactive T cells can be revealed in vivo, and                      whether a potent suppressive system down-regulates the cells in                 vivo.  Lastly, antibodies will be raised against the Xenopus T                  cell receptor, and isoelectric-focusing experiments will be                     performed to determine directly the impact of the thymus on the                 maturation of the T cell repertoire.                                                                                                                            Although studies of the immune response in mammals and the human                have received much attention, studies in lower vertebrates have                 been pursued less actively even though these organisms provide                  some unique opportunities to advance our understanding of the                   evolution and development of mechanisms of self recognition and                 self defense.  This research takes advantage of some unique                     features of the development of the frog to approach the question                of how amphibian lymphocytes are programmed genetically and                     developmentally to distinguish appropriate (foreign) target cells               from inappropriate (self) target cells.  The results of this                    study will enhance our basic understanding of defense responses                 in a diversity of organisms.
{'FirstName': 'Martin', 'LastName': 'Flajnik', 'PI_MID_INIT': 'F', 'PI_SUFX_NAME': None, 'PI_FULL_NAME': 'Martin F Flajnik', 'EmailAddress': '3055484857', 'NSF_ID': '000215810', 'StartDate': '09/01/1989', 'EndDate': None, 'RoleCode': 'Principal Investigator'}
{'Name': 'University of Miami School of Medicine', 'CityName': 'CORAL GABLES', 'ZipCode': '331462926', 'PhoneNumber': '3052843924', 'StreetAddress': '1320 S DIXIE HWY STE 1200', 'StreetAddress2': None, 'CountryName': 'United States', 'StateName': 'Florida', 'StateCode': 'FL', 'CONGRESSDISTRICT': '27', 'CONGRESS_DISTRICT_ORG': 'FL27', 'ORG_UEI_NUM': 'F8THLJQSAF93', 'ORG_LGL_BUS_NAME': 'UNIVERSITY OF MIAMI', 'ORG_PRNT_UEI_NUM': None}
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[{'Code': '1114', 'Text': 'Cellular Dynamics and Function'}, {'Code': '9145', 'Text': 'SPECIAL PROGRAMS-RESERVE'}]
{'url': 'https://www.nsf.gov/awardsearch/download?DownloadFileName=1988&All=true', 'xml': '8819366.xml'}