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Phenotype and function of the memory CD8 T cells generated by different protocols of vaccination against experimental infection with Trypanosoma cruzi

Grant number: 06/01983-4
Support type:Regular Research Grants
Duration: August 01, 2006 - July 31, 2009
Field of knowledge:Biological Sciences - Immunology
Principal Investigator:Maurício Martins Rodrigues
Grantee:Maurício Martins Rodrigues
Home Institution: Departamento de Microbiologia, Imunologia e Parasitologia. Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil

Abstract

In recent years, we demonstrated that the vaccination with genes/antigens of Trypanosoma cruzi generates specific memory CD8+ T cells which contribute decisively to the immunity against experimental chagasic infection. In spite the fact that we have established the role of these cells during the protective immunity, little is known about their phenotypic and functional characteristics. The overall objective of this project will be the characterization of immune-protective specific memory CD8+ T cells induced by different protocols of vaccination against experimental infection caused by T. cruzi.Our experimental approach will consist in the immunization of A/Sn (or if necessary B10.A or C3H/HeJ) mice with different vectors (plasmidial DNA, recombinant proteins and recombinant virus) expressing the gene/protein of ASP-2 (amastigote surface protein-2) of T. cruzi. The CD8+ T cells specific to the epitope TEWETGQI will be evaluated by different phenotypic and functional parameters following vaccination, before and after a challenge with T. cruzi. We believe that our results will contribute to the comprehension of the function of the immune-protective specific memory CD8+ T cells generated during vaccinantion against experimental infection caused by T. cruzi. The phenotypic and functional markers of the mice immune-protective specific memory CD8+ T cells may assist during human immunizations because in that case it will be not possible to determine the protective immunity through experimental challenges.Specific aims:1- Comparison of the longevity of the protective immune response in mice immunized with different vectors (plasmidial DNA, recombinant proteins and recombinant virus).2- Comparison of the immune response mediated by CD8+ T cells specific to the epitope TEWETGQI after different periods after the last immuning dose.3- Determination of the phenotype of the specific CD8+ T cells following vaccination, before and after challenge with T. cruzi.4- Characterization of the function of CD8+ specific T cells following vaccination, before and after challenge with T. cruzi. (AU)