title: Mycobacterial Hsp65 antigen upregulates the cellular immune response of healthy individuals compared with tuberculosis patients.
abstract: Previously we showed that 65-kDa Mycobacterium leprae heat shock protein (Hsp65) is a target for the development of a tuberculosis vaccine. Here we evaluated peripheral blood mononuclear cells (PBMC) from healthy individuals or tuberculosis patients stimulated with two forms of Hsp65 antigen, recombinant DNA that encodes Hsp65 (DNA-HSP65) or recombinant Hsp65 protein (rHsp65) in attempting to mimic a prophylactic or therapeutic study in vitro, respectively. Proliferation and cytokine-producing CD4+or CD8+cell were assessed by flow cytometry. The CD4+cell proliferation from healthy individuals was stimulated by DNA-HSP65 and rHsp65, while CD8+cell proliferation from healthy individuals or tuberculosis patients was stimulated by rHSP65. DNA-HSP65 did not improve the frequency of IFN-gamma+cells from healthy individuals or tuberculosis patients. Furthermore, we found an increase in the frequency of IL-10-producing cells in both groups. These findings show that Hsp65 antigen activates human lymphocytes and plays an immune regulatory role that should be addressed as an additional antigen for the development of antigen-combined therapies.
authors.affiliation: a Department of Biochemistry and Immunology , Ribeirão Preto Medical School, University of São Paulo , Ribeirão Preto , Brazil.
authors.forename: Pryscilla Fanini
authors.initials: PF
authors.lastname: Wowk
authors.affiliation: a Department of Biochemistry and Immunology , Ribeirão Preto Medical School, University of São Paulo , Ribeirão Preto , Brazil.
authors.forename: Luís Henrique
authors.initials: LH
authors.lastname: Franco
authors.affiliation: a Department of Biochemistry and Immunology , Ribeirão Preto Medical School, University of São Paulo , Ribeirão Preto , Brazil.
authors.forename: Denise Morais da
authors.initials: DMD
authors.lastname: Fonseca
authors.affiliation: a Department of Biochemistry and Immunology , Ribeirão Preto Medical School, University of São Paulo , Ribeirão Preto , Brazil.
authors.forename: Marina Oliveira
authors.initials: MO
authors.lastname: Paula
authors.affiliation: b Respiratory Division, School of Medicine of Ribeirão Preto, University of São Paulo , São Paulo , Ribeirão Preto , Brazil.
authors.forename: Élcio Dos Santos Oliveira
authors.initials: ÉDSO
authors.lastname: Vianna
authors.affiliation: c Laboratory of Biomarkers for Diagnosis and Monitoring , René Rachou Research Center , Fiocruz, Belo Horizonte , Minas Gerais , Brazil.
authors.forename: Ana Paula
authors.initials: AP
authors.lastname: Wendling
authors.affiliation: d Federal University of Minas Gerais , Belo Horizonte , Brazil.
authors.forename: Valéria Maria
authors.initials: VM
authors.lastname: Augusto
authors.affiliation: d Federal University of Minas Gerais , Belo Horizonte , Brazil.
authors.forename: Silvana Maria
authors.initials: SM
authors.lastname: Elói-Santos
authors.affiliation: c Laboratory of Biomarkers for Diagnosis and Monitoring , René Rachou Research Center , Fiocruz, Belo Horizonte , Minas Gerais , Brazil.
authors.forename: Andréa
authors.initials: A
authors.lastname: Teixeira-Carvalho
authors.affiliation: e Mycobacteriology Laboratory, Nucleus of Infectious Diseases , Federal University of Espírito Santo , Vitória , Espírito Santos , Brazil.
authors.forename: Flávia Dias Coelho
authors.initials: FDC
authors.lastname: Silva
authors.affiliation: e Mycobacteriology Laboratory, Nucleus of Infectious Diseases , Federal University of Espírito Santo , Vitória , Espírito Santos , Brazil.
authors.forename: Solange Alves
authors.initials: SA
authors.lastname: Vinhas
authors.affiliation: c Laboratory of Biomarkers for Diagnosis and Monitoring , René Rachou Research Center , Fiocruz, Belo Horizonte , Minas Gerais , Brazil.
authors.forename: Olindo Assis
authors.initials: OA
authors.lastname: Martins-Filho
authors.affiliation: e Mycobacteriology Laboratory, Nucleus of Infectious Diseases , Federal University of Espírito Santo , Vitória , Espírito Santos , Brazil.
authors.forename: Moisés
authors.initials: M
authors.lastname: Palaci
authors.affiliation: a Department of Biochemistry and Immunology , Ribeirão Preto Medical School, University of São Paulo , Ribeirão Preto , Brazil.
authors.forename: Célio Lopes
authors.initials: CL
authors.lastname: Silva
authors.affiliation: a Department of Biochemistry and Immunology , Ribeirão Preto Medical School, University of São Paulo , Ribeirão Preto , Brazil.
authors.forename: Vânia Luiza Deperon
authors.initials: VLD
authors.lastname: Bonato
mesh_terms: D000328:Adult; D001426:Bacterial Proteins / Q000235:genetics / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D018834:Chaperonin 60 / Q000235:genetics / Q000276:immunology*; D003602:Cytotoxicity, Immunologic; D005260:Female; D064368:Healthy Volunteers; D006801:Humans; D007111:Immunity, Cellular; D007371:Interferon-gamma / Q000096:biosynthesis / Q000276:immunology; D016753:Interleukin-10 / Q000096:biosynthesis / Q000276:immunology; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008213:Lymphocyte Activation; D016676:Macrophages, Alveolar / Q000276:immunology; D008297:Male; D008875:Middle Aged; D009169:Mycobacterium tuberculosis / Q000276:immunology; D011994:Recombinant Proteins / Q000276:immunology; D014376:Tuberculosis / Q000276:immunology*; D032581:Tuberculosis Vaccines / Q000276:immunology; D015854:Up-Regulation; D019444:Vaccines, DNA / Q000494:pharmacology; D055815:Young Adult
chemical_list: D001426:Bacterial Proteins; D018834:Chaperonin 60; D011994:Recombinant Proteins; D032581:Tuberculosis Vaccines; D019444:Vaccines, DNA; C074119:heat-shock protein 65, Mycobacterium; D016753:Interleukin-10; D007371:Interferon-gamma
keywords: IFN-γ; IL-10; tuberculosis; vaccine