D. Elias et al., INDUCTION OF DIABETES IN STANDARD MICE BY IMMUNIZATION WITH THE P277 PEPTIDE OF A 60-KDA HEAT-SHOCK PROTEIN, European Journal of Immunology, 25(10), 1995, pp. 2851-2857
We previously reported that immunity to the p277 peptide of the human
60-kDa heat shock protein (hsp60) was a causal factor in the diabetes
of non-obese diabetic (NOD) mice, which are genetically prone to devel
op spontaneous autoimmune diabetes. The present study was done to test
whether immunization with the p277 peptide could cause diabetes in st
andard strains of mice. We now report that a single administration of
the p277 peptide conjugated to carrier molecules such as bovine serum
albumin or ovalbumin can induce diabetes in C57BL/6 mice and in other
strains not genetically prone to develop diabetes. The diabetes was ma
rked by hyperglycemia, insulitis, insulin autoantibodies, glucose into
lerance and low blood levels of insulin. The diabetes could be transfe
rred to naive recipients by anti-p277 T cell lines. Similar to other e
xperimentally induced autoimmune diseases, the autoimmune diabetes rem
itted spontaneously. After recovery, the mice were found to have acqui
red resistance to a second induction of diabetes. Susceptibility to in
duced diabetes in C57BL/6 mice was influenced by sex (males were much
more susceptible than were females) and by class II genes in the major
histocompatibility complex (B6.H-2(bm12) mice with a mutation in the
MHC-II molecule were relatively resistant). Other strains of mice susc
eptible to induced diabetes were C57BL/KSJ, C3HeB/FeJ, and NON/Lt. BAL
B/c and C3H/HeJ strains were relatively resistant. Immunization to p27
7-carrier conjugates could also induce transient hyperglycemia in youn
g NOD mice, but upon recovery from the induced diabetes, the NOD mice
were found to have acquired resistance to later development of spontan
eous diabetes. Thus, T cell immunity to the p277 peptide can suffice t
o induce diabetes in standard mice, and a short bout of induced diabet
es can affect the chronic process that would otherwise lead to spontan
eous diabetes in diabetes-prone NOD mice.