DNA vaccine containing the mycobacterial hsp65 gene prevented insulitis in MLD-STZ diabetes

• Autor(a) principal: Santos Junior, Rubens R. [UNESP]
• Data de Publicação: 2009
• Outros Autores: Sartori, Alexandrina [UNESP], Lima, Deison S., Souza, Patrícia R.M., Coelho-Castelo, Arlete A.M., Bonato, Vânia L.D., Silva, Célio L.
• Tipo de documento: Artigo
• Idioma: eng
• Título da fonte: Repositório Institucional da UNESP
• Texto Completo: http://dx.doi.org/10.1186/1476-8518-7-4; http://hdl.handle.net/11449/71151
• topic: 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

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.