Immune regulatory effect of pHSP65 DNA therapy in pulmonary tuberculosis: Activation of CD8+ cells, interferon-γ recovery and reduction of lung injury

• Autor(a) principal: Bonato, V. L D
• Data de Publicação: 2004
• Outros Autores: Gonçalves, E. D C, Soares, E. G., Santos, R. R., Sartori, A. [UNESP], Coelho-Castelo, A. A M, Silva, C. L.
• Tipo de documento: Artigo
• Idioma: eng
• Título da fonte: Repositório Institucional da UNESP
• Texto Completo: http://dx.doi.org/10.1111/j.1365-2567.2004.01931.x; http://hdl.handle.net/11449/67846
• topic: Interferon-γ; Mycobacterium tuberculosis; pHSP65 DNA therapy; Protection; T CD8+ lymphocytes; CD8 antigen; DNA vaccine; gamma interferon; heat shock protein; synaptotagmin; animal experiment; animal model; animal tissue; cell activation; cellular immunity; controlled study; drug effect; drug mechanism; evaluation; female; immune response; immunoregulation; immunotherapy; lung injury; lung tuberculosis; mouse; nonhuman; priority journal; treatment outcome; Animals; Antigens, CD18; Antigens, CD28; Antigens, CD95; Bacterial Proteins; CD4-Positive T-Lymphocytes; CD8-Positive T-Lymphocytes; Chaperonins; Fas Ligand Protein; Female; Interferon Type II; Lymphocyte Activation; Membrane Glycoproteins; Mice; Mice, Inbred BALB C; Tuberculosis, Pulmonary; Up-Regulation; Vaccines, DNA

A DNA vaccine based on the heat-shock protein 65 Mycobacterium leprae gene (pHSP65) presented a prophylactic and therapeutic effect in an experimental model of tuberculosis. In this paper, we addressed the question of which protective mechanisms are activated in Mycobacterium tuberculosis-infected mice after immune therapy with pHSP65. We evaluated activation of the cellular immune response in the lungs of infected mice 30 days after infection (initiation of immune therapy) and in those of uninfected mice. After 70 days (end of immune therapy), the immune responses of infected untreated mice, infected pHSP65-treated mice and infected pCDNA3-treated mice were also evaluated. Our results show that the most significant effect of pHSP65 was the stimulation of CD8+ lung cell activation, interferon-γ recovery and reduction of lung injury. There was also partial restoration of the production of tumour necrosis factor-α. Treatment with pcDNA3 vector also induced an immune stimulatory effect. However, only infected pHSP65-treated mice were able to produce significant levels of interferon-γ and to restrict the growth of bacilli.