D. Elias et al., HSP60 PEPTIDE THERAPY OF NOD MOUSE DIABETES INDUCES A TH2 CYTOKINE BURST AND DOWN-REGULATES AUTOIMMUNITY TO VARIOUS BETA-CELL ANTIGENS, Diabetes, 46(5), 1997, pp. 758-764
A peptide of the human BO-kDa heat-shock protein (hsp60), designated p
277, was found to be useful as a therapeutic agent to arrest the autoi
mmune process responsible for diabetes in nonobese diabetic (NOD) mice
. The effectiveness of peptide treatment was associated with the induc
tion of peptide-specific antibodies of the IgG1 but not of the IgG2a i
sotype, suggesting the possibility that a Th2-type response may have b
een induced. We now report that the effectiveness of p277 treatment is
associated with the transient activation of anti-p277 splenic T-cells
that produce the Th2 cytokines interleukin-4 (IL-4) and IL-10. The Th
2 response to p277 was associated with reduced Th1-type autoimmunity t
o hsp60 and to two other target antigens associated with diabetes: GAD
and insulin. The Th2 shift appeared to be relatively specific; sponta
neous T-cell reactivity to a bacterial antigen peptide remained in the
Th1 mode in the p277-treated mice. Moreover, treatment with the bacte
rial peptide did not induce a change in cytokine profile, and it did n
ot affect progression of the disease. Thus, effective peptide treatmen
t of the diabetogenic process associated with the induction of antibod
ies may be explained by selective and transient activation of Th2 auto
immune reactivity.