Sp. Barrett et al., EXPRESSION OF A GASTRIC AUTOANTIGEN IN PANCREATIC-ISLETS RESULTS IN NONDESTRUCTIVE INSULITIS AFTER NEONATAL THYMECTOMY, European Journal of Immunology, 25(9), 1995, pp. 2686-2694
Autoimmune gastritis, induced by day-3 thymectomy of BALB/c mice, is a
destructive CD4(+) T cell-mediated disease characterized by leukocyte
infiltrates in the gastric mucosa, loss of parietal and chief cells a
nd anti-gastric H/K ATPase autoantibodies. Our previous studies have i
ndicated that a T cell response to the WK ATPase beta subunit is requi
red for the onset of autoimmune gastritis (Alderuccio, F, Toh, B. H,,
Tan, S. S., Gleeson, P. A. and van Driel, I. R., J. Exp. Med. 1993. 17
8: 419). To determine whether a response to the beta subunit autoantig
en is alone sufficient to induce autoimmunity, or whether other tissue
-specific factors are required, we have generated transgenic mice expr
essing the gastric WK ATPase beta subunit in beta islet cells of the p
ancreas (RIP-H/K beta). RIP-H/K beta mice developed autoimmune gastrit
is and insulitis after day-3 thymectomy. Significantly, insulitis, obs
erved as a peri-islet infiltrate, was only detected in thymectomized m
ice with autoimmune gastritis. There was no apparent immune destructio
n of the pancreas as insulitis did not progress to invasion of the isl
ets or diabetes. Double transgenic mice, expressing the gastric WK ATP
ase beta subunit in the thymus and in the pancreas, were protected fro
m both gastritis and insulitis after day-3 thymectomy. Therefore, insu
litis in the RIP-H/K beta mice appears to be dependent on a T cell res
ponse to the WI ATPase beta subunit. This is the first example where a
n organ-specific initiating autoantigen has been expressed in another
peripheral tissue. Autoimmune destruction in the stomach, but not the
pancreas, indicates that tissue-specific factors play a fundamental ro
le in the development of organ-specific autoimmunity.