title: Immune modulation induced by tuberculosis DNA vaccine protects non-obese diabetic mice from diabetes progression.
abstract: 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 beta 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.
authors.affiliation: Núcleo de Pesquisas em Tuberculose, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Brazil.
authors.forename: R Rodrigues dos
authors.initials: RR
authors.lastname: Santos Júnior
authors.forename: A
authors.initials: A
authors.lastname: Sartori
authors.forename: V L Deperon
authors.initials: VL
authors.lastname: Bonato
authors.forename: A A M
authors.initials: AA
authors.lastname: Coelho Castelo
authors.forename: C A
authors.initials: CA
authors.lastname: Vilella
authors.forename: R L
authors.initials: RL
authors.lastname: Zollner
authors.forename: C Lopes
authors.initials: CL
authors.lastname: Silva
mesh_terms: D000818:Animals; D000907:Antibodies, Bacterial / Q000096:biosynthesis; D001324:Autoantigens / Q000276:immunology; D001426:Bacterial Proteins / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D018834:Chaperonin 60; D018833:Chaperonins / Q000276:immunology; D003922:Diabetes Mellitus, Type 1 / Q000517:prevention & control*; D018450:Disease Progression; D007074:Immunoglobulin G / Q000096:biosynthesis; D016753:Interleukin-10 / Q000378:metabolism; D053645:Interleukin-2 Receptor alpha Subunit / Q000032:analysis; D007515:Islets of Langerhans / Q000276:immunology; D051379:Mice; D016688:Mice, Inbred NOD; D032581:Tuberculosis Vaccines / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D019444:Vaccines, DNA / Q000276:immunology
chemical_list: D000907:Antibodies, Bacterial; D001324:Autoantigens; D001426:Bacterial Proteins; D018834:Chaperonin 60; D007074:Immunoglobulin G; D053645:Interleukin-2 Receptor alpha Subunit; D032581:Tuberculosis Vaccines; D014409:Tumor Necrosis Factor-alpha; D019444:Vaccines, DNA; C074119:heat-shock protein 65, Mycobacterium; D016753:Interleukin-10; D018833:Chaperonins