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

The fate of autoreactive CD4 +T cells was investigated in HNT-TCR×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×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 naı̈ve phenotype and were neither deleted nor anergized. Finally, immunization of HNT-TCR×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.