Immune modulation induced by tuberculosis DNA vaccine protects non‐obese diabetic mice from diabetes progression

Summary We have described previously the prophylactic and therapeutic effect of a DNA vaccine encoding the Mycobacterium leprae 65 kDa heat shock protein (DNA‐HSP65) in experimental murine tuberculosis. However, the high homology of this protein to the corresponding mammalian 60 kDa heat shock prote...

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Published in:	Clinical and experimental immunology Vol. 149; no. 3; pp. 570 - 578
Main Authors:	Rodrigues dos Santos, R., Sartori, A., Deperon Bonato, V. L., Coelho Castelo, A. A. M., Vilella, C. A., Zollner, R. L., Lopes Silva, C.
Format:	Journal Article
Language:	English
Published:	Oxford, UK Blackwell Publishing Ltd 01-09-2007 Blackwell Blackwell Science Inc
Subjects:	Analytical, structural and metabolic biochemistry Animals Antibodies, Bacterial - biosynthesis Autoantigens - immunology Bacterial Proteins - immunology Biological and medical sciences CD4-Positive T-Lymphocytes - immunology CD8-Positive T-Lymphocytes - immunology Chaperonin 60 Chaperonins - immunology cytokines diabetes Diabetes Mellitus, Type 1 - prevention & control Disease Progression DNA vaccine Fundamental and applied biological sciences. Psychology heat shock protein (Hsp65) Immunoglobulin G - biosynthesis Interleukin-10 - metabolism Interleukin-2 Receptor alpha Subunit - analysis Islets of Langerhans - immunology Mice Mice, Inbred NOD Molecular biophysics Mycobacterium Mycobacterium leprae Translational Studies Tuberculosis Vaccines - immunology Tumor Necrosis Factor-alpha - metabolism Vaccines, DNA - immunology Endocrinopathy DNA vaccine Immunomodulation Diabetes mellitus Cytokine Biochemistry Mycobacterial infection Biophysics Genetic vaccine Infection heat shock protein (Hsp65) Treatment Tuberculosis Immunotherapy Heat shock protein Heat shock protein 65 Bacteriosis cytokines Non obese diabetic mouse Molecular biology Protection diabetes
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Summary:	Summary We have described previously the prophylactic and therapeutic effect of a DNA vaccine encoding the Mycobacterium leprae 65 kDa heat shock protein (DNA‐HSP65) in experimental murine tuberculosis. However, the high homology of this protein to the corresponding mammalian 60 kDa heat shock protein (Hsp60), together with the CpG motifs in the plasmid vector, could trigger or exacerbate the development of autoimmune diseases. The non‐obese diabetic (NOD) mouse develops insulin‐dependent diabetes mellitus (IDDM) spontaneously as a consequence of an autoimmune process that leads to destruction of the insulin‐producing β cells of the pancreas. IDDM is characterized by increased T helper 1 (Th1) cell responses toward several autoantigens, including Hsp60, glutamic acid decarboxylase and insulin. In the present study, we evaluated the potential of DNA‐HSP65 injection to modulate diabetes in NOD mice. Our results show that DNA‐HSP65 or DNA empty vector had no diabetogenic effect and actually protected NOD mice against the development of severe diabetes. However, this effect was more pronounced in DNA‐HSP65‐injected mice. The protective effect of DNA‐HSP65 injection was associated with a clear shift in the cellular infiltration pattern in the pancreas. This change included reduction of CD4+ and CD8+ T cells infiltration, appearance of CD25+ cells influx and an increased staining for interleukin (IL)‐10 in the islets. These results show that DNA‐HSP65 can protect NOD mice against diabetes and can therefore be considered in the development of new immunotherapeutic strategies.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0009-9104 1365-2249
DOI:	10.1111/j.1365-2249.2007.03433.x