F. Colucci et al., NON-DIABETOGENIC INSULITIS IN NOD[--]B1O.GD ALLOPHENIC MICE IN SPITE OF PERMISSIVE CLASS-I MHC ANTIGENS, Scandinavian journal of immunology, 40(6), 1994, pp. 659-664
Allophenic mice (embryo aggregation mouse chimeras) enable us to disse
ct the process of spontaneous autoimmunity under physiological conditi
ons. Our previous experiments showed that the autoimmune process in al
lophenic mice of the NOD<->C57B1/6 strain combination does not progres
s from insulitis to diabetes. One possible explanation for this protec
tion is that H-2 K-d-restricted CD8(+) T cells kill only NOD beta cell
s (K-d, D-b) in the chimeric islets, while the B6 beta cells (K-b, D-b
) are spared from destruction. To test this hypothesis we analysed 22
NOD<->B10.GD chimeras in which the class I MHC are shared by both pare
ntal strains. Therefore all the beta cells in these chimeras express H
-2 K-d molecules. Ten allophenic mice were killed at 7 weeks and studi
ed for early pathology. No evidence for intra-islet infiltration was o
btained at this age, suggesting that the autoimmune process in NOD<->B
10.GD chimeras is slower than in NOD mice. Twelve chimeras were follow
ed up for 1 year for disease development and all failed to progress to
full-blown diabetes, despite the occurrence of intra-insulitis in six
out of 12 mice. The lack of disease in NOD<->B10.GD chimeras demonstr
ates that class I MHC chimerism does not account for diabetes resistan
ce in NOD-allophenic mice.