DiaPep277 May Work Orally to Assist
Conversion of Helper to Suppressor Th2 Cells
in Models of Type 1 Diabetes
S. Brugman1,
J. Visser1, F. Klatter1, D. Elias2, N. Bos1, J. Rozing1;
1Cell Biology, University of Groningen, Groningen, Netherlands,
2Peptor Ltd., Revohot, Israel.
Background and Aims: Diabetes Type 1 is an
autoimmune disease that leads to the destruction of
insulin-producing ß-cells in the islets of Langerhans in the
pancreas. The identity of the target self-antigen
is not known. Several self-antigens have been reported to be
involved in activating T-cells to destroy the
islets. Hsp60 is one of those self-antigens. Heat shock proteins
are found in all life forms and are highly
conserved. Hsp60 (the human equivalent of bacterial hsp65) has
been implicated in autoimmunity through
molecular mimicry, based on the high homology with hsp65 of
microorganisms leading to recognition of
the hsp60 and consequent reaction of the immune system. DiaPep277
is composed of a 24-amino-acid
sequence of hsp60. NOD mice spontaneously developing diabetes
manifest progressive T-cell reactivity
to p277 beginning at the onset of insulitis. The objective of the
present study was to test whether it was
possible to affect diabetes development by neonatal oral
administration of DiaPep277 in two models of
diabetes; the BB-DP rat model and BB-DP rats on a hydrolysed
casein (HC) diet, which gives partial
protection against diabetes.
Materials and Methods: Neonatal BB-DP rats
received orally either DiaPep277 in saline or saline on day
4, 5, 6, and 7 of life (300 µg/rat/day). After weaning, rats
received either standard laboratory chow or HC
diet.
Results: The group that received DiaPep277 and
standard chow showed a lower diabetes incidence
(69% DiaPep277 versus 86% in control). The DiaPep277 and HC diet
group showed an even lower
incidence (31% Diapep277 + HC compared to 53% in control + HC).
As previously reported, groups that
received HC diet showed a delay in onset of diabetes (from the
age of 60 days in the control groups to an
average 80 days in the HC groups). Analysis of the intestinal
flora of the animals showed a significant
increase in Eubacterium sp. in the HC groups. No differences were
found between the groups receiving
DiaPep277 or saline.
Conclusion: While HC diets could have their
protective effects by changing the composition of intestinal
microflora, DiaPep277 could have its effect through induction of
oral tolerance.
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