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Publication : A transgenic mouse model for T-cell ignorance of a glial autoantigen.

First Author  Cabarrocas J Year  2004
Journal  J Autoimmun Volume  22
Issue  3 Pages  179-89
PubMed ID  15041038 Mgi Jnum  J:90579
Mgi Id  MGI:3044248 Doi  10.1016/j.jaut.2004.01.001
Citation  Cabarrocas J, et al. (2004) A transgenic mouse model for T-cell ignorance of a glial autoantigen. J Autoimmun 22(3):179-89
abstractText  The fate of autoreactive CD4+T cells was investigated in HNT-TCR x GFAP-HA double transgenic mice, in which the majority of CD4+T cells is specific for a neo-selfantigen expressed under a glial cell-specific promoter. These mice do not develop any clinical or histological signs of central or enteric nervous system autoimmunity. Although HA is transcribed in the thymus of GFAP-HA mice, similar numbers of CD4+ CD8- thymocytes, expressing comparable levels of the transgenic TCR, developed in HNT-TCR x GFAP-HA double transgenic and HNT-TCR single transgenic mice, indicating that HA-specific thymocytes are not negatively selected. In the periphery, the HA-specific T cells remained similarly unaffected as they displayed a naive phenotype and were neither deleted nor anergized. Finally, immunization of HNT-TCR x GFAP-HA mice with the HNT peptide in CFA and/or in vivo depletion of CD25+ cells did not reverse this state of immune ignorance as judged by the lack of clinical manifestations of intestinal and neurological disease in these mice. Taken together these data demonstrate a profound state of immune ignorance towards a self-antigen expressed in the enteric and central nervous system.
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