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Role of specific CD4+ and CD8+ T cells generated by different vaccination protocols against experimental Trypanosoma cruzi infection

Grant number: 18/15607-1
Support type:Research Grants - Young Investigators Grants- Phase 2
Duration: May 01, 2019 - April 30, 2024
Field of knowledge:Biological Sciences - Immunology
Principal Investigator:Jose Ronnie Carvalho de Vasconcelos
Grantee:Jose Ronnie Carvalho de Vasconcelos
Home Institution: Instituto de Saúde e Sociedade (ISS). Universidade Federal de São Paulo (UNIFESP). Campus Baixada Santista. Santos , SP, Brazil
Assoc. researchers:Alexandre de Magalhães Vieira Machado ; Karina Ramalho Bortoluci ; MARIA BELLIO ; Thiago Mattar Cunha
Associated research grant:12/22514-3 - Migration study of specific T cells generated by vaccination or Trypanosoma cruzi infection, AP.JP


Natural infection by the intracellular protozoan Trypanosoma cruzi, the causative agent of Chagas' disease, induces an immune response in the mammalian host that counts on the participation of innate and adaptive immunity. Our group demonstrated that heterologous genetic immunization with ASP-2 and/or trans-sialidase from T. cruzi generates a protective response against different models of experimental infection. This protocol induces strong cell mediated immunity (CMI) in which the specific CD4+ and CD8+ T cells are a critical. In addition, we have shown that CD8+ T cells have phenotypic and functional characteristics of effector memory T cells (TEM) and need to recirculate to exert protective immune responses in non-lymphoid peripheral tissues. Results obtained during the Young Researcher phase 1 project showed that the LFA-1 molecule plays a critical role in the migration of CD8+ T cells generated by heterologous genetic vaccination (Ferreira et al., 2017) as well as the CXCR3 molecule. In addition, specific CD8+ T cells from infected mice showed high expression of the chemokine receptor CX3CR1. It has recently been described that this molecule defines three subpopulations of CD8+ T cells during viral infections and is related to the differentiation in effector CD8+ T cells. Although CD4+ T cells play a key role in protective immunity, few papers show a detailed study of the role of specific CD4+ T cells generated by immunization or infection. In view of this, the overall objective of this project will be to study the phenotype and cytotoxic function of specific CD4+ T cells (CD4CTLs) using recombinant fd filamentous phage (rfd) as vaccine vectors, and the role of CXCR3 and CX3CR1 chemokine receptors in the activation and differentiation of specific CD8+ T cells after heterologous genetic immunization with ASP-2 and/or trans-sialidase from T. cruzi. (AU)

Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
FERREIRA, CAMILA PONTES; CARISTE, LEONARDO MORO; MORASCHI, BARBARA FERRI; ZANETTI, BIANCA FERRARINI; HAN, SANG WON; RIBEIRO, DANIEL ARAKI; MACHADO, ALEXANDRE VIEIRA; LANNES-VIEIRA, JOSELI; GAZZINELLI, RICARDO TOSTES; CARVALHO VASCONCELOS, JOSE RONNIE. CXCR3 chemokine receptor guides Trypanosoma cruzi-specific T-cells triggered by DNA/adenovirus ASP2 vaccine to heart tissue after challenge. PLoS Neglected Tropical Diseases, v. 13, n. 7 JUL 2019. Web of Science Citations: 0.

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