Predominance of CD4 Th1 and CD8 Tc1 cells revealed by characterization of the cellular immune response generated by immunization with a DNA vaccine containing a Trypanosoma cruzi gene

Predominance of CD4 Th1 and CD8 Tc1 cells revealed by characterization of the cellular immune response generated by immunization with a DNA vaccine containing a Trypanosoma cruzi gene

Author Rodrigues, Mauricio Martins Autor UNIFESP Google Scholar
Ribeirao, Marcelo Autor UNIFESP Google Scholar
Pereira-Chioccola, Vera Lucia Autor UNIFESP Google Scholar
Renia, Laurent Google Scholar
Costa, Fabio Autor UNIFESP Google Scholar
Institution Universidade Federal de São Paulo (UNIFESP)
Inst Dante Pazzanese Cardiol Estado Sao Paulo
Univ Paris 05
Abstract Immunization with a plasmid DNA containing the gene encoding the catalytic domain of trans-sialidase (TS) elicits protective immune responses against experimental Trypanosoma cruzi infection. As several studies provided strong evidence that during infection CD4 Th1 and CD8 T cytotoxic type 1 (Tc1) cells are important factors in host resistance, the present study was designed to evaluate which T-cell types were activated in DNA-vaccinated BALB/c mice. We found that bulk cells from DNA-immunized mice had CD4 and CD8 T cells that produced gamma interferon (IFN-gamma) but not interleukin-4 (IL-4) or IL-10. To characterize the TS-specific T cells at the clonal level, we generated CD4 and CD8 clones. We obtained cytotoxic CD4 clones of the Th1 type that secreted large amounts of IFN-gamma but not IL-4 or IL-10. Unexpectedly, we obtained other CD4 clones with a Th2 phenotype, secreting IL-4 and IL-10 but not IFN-gamma. All CD8 clones were cytotoxic and produced IFN-gamma. IL-4 and IL-10 were not secreted by these cells. Using synthetic peptides, we determined a CDS epitope recognized by several clones as being represented by amino acids IYNVGQVSI. The antiparasitic activity of a CD4 Th1 and a CDS Tc1 clone was assessed in vitro. CD4 or CD8 T cells significantly inhibited T. cruzi development in infected macrophages or fibroblasts, respectively. We concluded that DNA vaccine efficiently generates potentially protective CD4 Th1 and CD8 Tc1 cells specific for a T. cruzi antigen, therefore reinforcing the possibility of using this strategy for developing a preventive or therapeutic vaccine against Chagas' disease.
Language English
Date 1999-08-01
Published in Infection And Immunity. Washington: Amer Soc Microbiology, v. 67, n. 8, p. 3855-3863, 1999.
ISSN 0019-9567 (Sherpa/Romeo, impact factor)
Publisher Amer Soc Microbiology
Extent 3855-3863
Origin http://iai.asm.org/content/67/8/3855.abstract
Access rights Closed access
Type Article
Web of Science ID WOS:000081637400023
URI http://repositorio.unifesp.br/11600/43968

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