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. Conclusion: 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. © 2009 Santos et al; licensee BioMed Central Ltd.



CD103 antigen, CD4 antigen, CD8 antigen, cytotoxic T lymphocyte antigen 4, DNA vaccine, heat shock protein 65, interleukin 10, interleukin 2 receptor alpha, monoclonal antibody, streptozocin, tumor necrosis factor alpha, animal cell, animal experiment, animal model, animal tissue, autoimmunity, CD8+ T lymphocyte, controlled study, cytokine production, DNA vector, immunomodulation, immunotherapy, insulitis, lymphocyte subpopulation, lymphocytic infiltration, male, mouse, Mycobacterium, nonhuman, pancreas islet, regulatory T lymphocyte, spleen, streptozocin diabetes, treatment outcome

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Journal of Immune Based Therapies and Vaccines, v. 7, p. 4-.