DNA vaccine containing the mycobacterial hsp65 gene prevented insulitis in MLD-STZ diabetes.
BACKGROUND
Our group previously demonstrated that a DNA plasmid encoding the mycobacterial 65-kDa heat shock protein (DNA-HSP65) displayed prophylactic and therapeutic effect in a mice model for tuberculosis. This protection was attributed to induction of a strong cellular immunity against HSP65. As specific immunity to HSP60 family has been detected in arthritis, multiple sclerosis and diabetes, the vaccination procedure with DNA-HSP65 could induce a cross-reactive immune response that could trigger or worsen these autoimmune diseases.


METHODS
In this investigation was evaluated the effect of a previous vaccination with DNA-HSP65 on diabetes development induced by Streptozotocin (STZ). C57BL/6 mice received three vaccine doses or the corresponding empty vector and were then injected with multiple low doses of STZ.


RESULTS
DNA-HSP65 vaccination protected mice from STZ induced insulitis and this was associated with higher production of IL-10 in spleen and also in the islets. This protective effect was also concomitant with the appearance of a regulatory cell population in the spleen and a decreased infiltration of the islets by T CD8+ lymphocytes. The vector (DNAv) also determined immunomodulation but its protective effect against insulitis was very discrete.


CONCLUSIONS
The data presented in this study encourages a further investigation in the regulatory potential of the DNA-HSP65 construct. Our findings have important implications for the development of new immune therapy strategies to combat autoimmune diseases.
Santos
Rubens R
RR
University of São Paulo, Ribeirão Preto Medical School, Department of Biochemistry and Immunology, Ribeirão Preto, São Paulo, Brazil. clsilva@fmrp.usp.br.
Sartori
Alexandrina
A
Lima
Deison S
DS
Souza
Patrícia Rm
PR
Coelho-Castelo
Arlete Am
AA
Bonato
Vânia Ld
VL
Silva
Célio L
CL