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.
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 CD8 epitope recognized by several clones as being represented by amino acids IYNVGQVSI. The antiparasitic activity of a CD4 Th1 and a CD8 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.
Rodrigues
M M
MM
Departmento de Microbiologia, Imunologia e Parasitologia, Universidade Federal de São Paulo-Escola Paulista de Medicina, São Paulo, Brazil. Rodriguesm.dmip@epm.br
Ribeirão
M
M
Pereira-Chioccola
V
V
Renia
L
L
Costa
F
F
D016475:3T3 Cells; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D005260:Female; D007111:Immunity, Cellular; D007114:Immunization; D007371:Interferon-gamma / Q000096:biosynthesis; D051379:Mice; D008807:Mice, Inbred BALB C; D010957:Plasmids; D016052:Protozoan Vaccines / Q000276:immunology*; D014349:Trypanosoma cruzi / Q000276:immunology*; D019444:Vaccines, DNA / Q000276:immunology*
D016052:Protozoan Vaccines; D019444:Vaccines, DNA; D007371:Interferon-gamma