S. Degermann et al., ON THE VARIOUS MANIFESTATIONS OF SPONTANEOUS AUTOIMMUNE DIABETES IN RODENT MODELS, European Journal of Immunology, 24(12), 1994, pp. 3155-3160
Autoimmune (type 1) diabetes mellitus in mouse, rat, and humans shares
several features, including T lymphocyte infiltration into pancreatic
islets and a dependence on permissive class II major histocompatibili
ty complex (MHC) alleles. We report here on an experimental model invo
lving mice that express influenza hemagglutinin (HA) under the control
of the insulin promoter and, at the same time, a transgenic class II
MHC-restricted T cell receptor (TcR) specific for an HA peptide. These
mice spontaneously develop islet infiltrates resembling those found i
n NOD mice and most animals become diabetic within 8 weeks of age. Bec
ause of the availability of a clonotypic TcR antibody, we can be confi
dent that the Ins-HA transgene does not induce any measurable alterati
ons in the vast majority of T cells with the transgenic TcR in primary
and secondary lymphoid organs. Continuous export of large numbers of
HA-specific lymphocytes from the thymus was not required for the manif
estation of the disease since mice thymectomized at 3 days after birth
still developed the disease albeit with smaller infiltrates.