title: A transgenic mouse model for T-cell ignorance of a glial autoantigen.
abstract: 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 naïve 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.
authors.affiliation: INSERM U563, Purpan University Hospital, Place Dr Baylac, Toulouse 31000, France.
authors.forename: Julie
authors.initials: J
authors.lastname: Cabarrocas
authors.forename: Eliane
authors.initials: E
authors.lastname: Piaggio
authors.forename: Jacques P
authors.initials: JP
authors.lastname: Zappulla
authors.forename: Sabine
authors.initials: S
authors.lastname: Desbois
authors.forename: Lennart T
authors.initials: LT
authors.lastname: Mars
authors.forename: Hans
authors.initials: H
authors.lastname: Lassmann
authors.forename: Roland S
authors.initials: RS
authors.lastname: Liblau
mesh_terms: D000818:Animals; D001324:Autoantigens / Q000276:immunology*; D015551:Autoimmunity / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D004195:Disease Models, Animal; D006649:Histocompatibility Antigens / Q000276:immunology; D051379:Mice; D008822:Mice, Transgenic; D009457:Neuroglia / Q000276:immunology*; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D015375:Receptors, Interleukin-2 / Q000276:immunology
chemical_list: D001324:Autoantigens; D006649:Histocompatibility Antigens; D011948:Receptors, Antigen, T-Cell; D015375:Receptors, Interleukin-2