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Infection and Immunity, August 1999, p. 3855-3863, Vol. 67, No. 8
0019-9567/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

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

Mauricio M. Rodrigues,1,* Marcelo Ribeirão,1 Vera Pereira-Chioccola,2 Laurent Renia,3 and Fabio Costa1

Departmento de Microbiologia, Imunologia e Parasitologia, Universidade Federal de São Paulo-Escola Paulista de Medicina,1 and Laboratório de Xenodiagnóstico, Instituto Dante Pazzanese de Cardiologia do Estado de São Paulo,2 São Paulo, Brazil, and U445 INSERM, Institut Cochin de Genétique Moleculaire, Laboratoire d'Immunologie des Pathologies Infectieuses et Tumorales, Université René Descartes, Hôpital Cochin 27, 75014 Paris, France3

Received 17 December 1998/Returned for modification 5 March 1999/Accepted 5 May 1999

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.

* Corresponding author. Mailing address: UNIFESP---Escola Paulista de Medicina, Rua Botucatu, 862, 6° andar, 04023-062, São Paulo, SP, Brazil. Phone and fax: (55) (11) 571-1095. E-mail: Rodriguesm.dmip{at}epm.br.

Infection and Immunity, August 1999, p. 3855-3863, Vol. 67, No. 8
0019-9567/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


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Copyright © 1999 by the American Society for Microbiology. All rights reserved.