B cells Can Modulate the CD8 Memory T Cell after DNA Vaccination Against Experimental Tuberculosis
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RESEARCH
GENETIC VACCINES AND THERAPY
Open Access
B cells Can Modulate the CD8 Memory T Cell after DNA Vaccination Against Experimental Tuberculosis Luciana P Almeida1, Ana PF Trombone1, Julio CC Lorenzi1, Carolina D Rocha1, Thiago Malardo1, Isabela C Fontoura1, Ana F Gembre1, Ricardo LL Silva1, Célio L Silva1, Ademilson P Castelo2, Arlete AM Coelho-Castelo1*
Abstract Background: Although B cells are important as antigen presenting cells (APC) during the immune response, their role in DNA vaccination models is unknown. Methods: In this study in vitro and in vivo experiments were performed to evaluate the ability of B cells to protect mice against Mycobacterium tuberculosis challenge. Results: In vitro and in vivo studies showed that B cells efficiently present antigens after naked plasmid pcDNA3 encoding M. leprae 65-kDa heat shock protein (pcDNA3-Hsp65) internalization and protect B knock-out (BKO) mice against Mycobacterium tuberculosis infection. pcDNA3-Hsp65-transfected B cells adoptively transferred into BKO mice rescued the memory phenotypes and reduced the number of CFU compared to wild-type mice. Conclusions: These data not only suggest that B cells play an important role in the induction of CD8 T cells but also that they improve bacterial clearance in DNA vaccine model.
Background DNA vaccines consist of the specific gene of interest cloned into a bacterial plasmid that is engineered for optimal expression in eukaryotic cells, thereby leading to protective immune responses. In contrast with subunit vaccines, in DNA vaccination the immunogen is synthesized within the host by cells that have taken up the antigen-encoding DNA. Consequently, DNA vaccines join the advantages of subunit vaccines with the ability to generate antigens endogenously making them accessible to presentation. Moreover, CpG motifs in bacterial DNA can elicit innate immune response via Toll-like receptor 9-dependent pathway interfering with T cell activation [1,2]. One intriguing aspect of DNA vaccination involves the mechanism by which the encoded antigen is processed and presented to the immune system. Studies with bone marrow-chimeric * Correspondence: [email protected] 1 Department of Biochemistry and Immunology, Medical School of Ribeirão Preto, University of São Paulo, Brazil Full list of author information is available at the end of the article
mice have suggested that bone marrow-derived APCs play a key role in the induction of the immune response after DNA vaccination [1]. We previously demonstrated that intramuscular (i.m.) delivery of pcDNA3 encoding M. leprae 65-kDa heat shock protein (pcDNA3-Hsp65) results in activation of immune response, as well as protection against virulent M. tuberculosis challenge [3,4]. Despite the efficacy of DNA vaccines delivered by i.m. injection, little is known about the tissue distribution of plasmid as well as the cells involved in the uptake of pcDNA3-HSP65 in vivo. We have previously shown that pcDNA3-HSP65 can be uptaken by B cells in vivo [5]. These findings greatly encouraged us to
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