A transgenic mouse model for T-cell ignorance of a glial autoantigen.
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.
Cabarrocas
Julie
J
INSERM U563, Purpan University Hospital, Place Dr Baylac, Toulouse 31000, France.
Piaggio
Eliane
E
Zappulla
Jacques P
JP
Desbois
Sabine
S
Mars
Lennart T
LT
Lassmann
Hans
H
Liblau
Roland S
RS
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
D001324:Autoantigens; D006649:Histocompatibility Antigens; D011948:Receptors, Antigen, T-Cell; D015375:Receptors, Interleukin-2