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Migration study of specific T cells generated by vaccination or Trypanosoma cruzi infection

Abstract

CD8+ T cells play a key role in protective immunity against intracellular pathogens, such as Trypanosoma cruzi, the causative agent of Chagas disease. Integrins, cell adhesion molecules (CAM) and chemokine receptors may play a critical role in this process allowing these cells migrate to non-peripheral lymphoid tissues to exert their effector function. Recently, we demonstrated that treatment with the drug FTY720, an immunomodulator that acts as a high-affinity agonist at the sphingosine 1-phosphate receptor-1 (S1P1) that inhibits the cell traffic an exit from lymph nodes (LN), led to retention of specific CD8+ T cells in both LN of C57BL/6 mice infected as in A/Sn mice vaccinated and infected, making them susceptible to infection. These results were the first experimental evidence that the recirculation of specific CD8+ T cells is important for effectuation the immune response in T. cruzi infection model (Domingues et al., 2012). In analysis of cell surface molecules specific CD8+ T cells generated by genetic vaccination with T. cruzi ASP-2, amastigote surface protein-2, we found increased expression of molecules LFA-1 and VLA-4 in these cells (Vasconcelos et al., 2012). In view of this, the overall goal of this project is to study the role of the integrins LFA-1 and VLA-4, CAM ICAM-1 and the chemokine receptors CCR5, CXCR3 and CXCR4 in the migration of CD8+ cells generated by specific genetic immunization with heterologous ASP-2 T. cruzi. To do so, we will treat these immunized and infected mice with antibodies in order to block these molecules and observe whether an increasing in susceptibility may occur. This study is very important for the development of vaccines in general, and if it can in fact occur demonstrates the importance of migration of T lymphocytes, and molecules that mediate this process on the immunity induced by vaccination of experimental heterologous prime-boost. (AU)

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Scientific publications (11)
(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)
MORASCHI, BARBARA FERRI; NORONHA, ISAU HENRIQUE; FERREIRA, CAMILA PONTES; CARISTE, LEONARDO M.; MONTEIRO, CAROLINE B.; DENAPOLI, PRISCILA; VRECHI, TALITA; PEREIRA, GUSTAVO J. S.; GAZZINELLI, RICARDO T.; LANNES-VIEIRA, JOSELI; RODRIGUES, MAURICIO M.; BORTOLUCI, KARINA R.; VASCONCELOS, JOSE RONNIE C. Rapamycin Improves the Response of Effector and Memory CD8(+) T Cells Induced by Immunization With ASP2 of Trypanosoma cruzi. FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY, v. 11, MAY 25 2021. Web of Science Citations: 0.
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.
PIDONE RIBEIRO, FLAVIA ANDRESSA; PONTES, CAMILA; MACHADO, ALEXANDRE DE M. V.; BRUNA-ROMERO, OSCAR; QUINTANA, HANANIAH T.; DE OLIVEIRA, FLAVIA; CARVALHO DE VASCONCELOS, JOSE RONNIE; RIBEIRO, DANIEL ARAKI. Therapeutical effects of vaccine from Trypanosoma cruzi amastigote surface protein 2 by simultaneous inoculation with live parasites. Journal of Cellular Biochemistry, v. 120, n. 3, p. 3373-3383, MAR 2019. Web of Science Citations: 0.
PIDONE RIBEIRO, FLAVIA ANDRESSA; PONTES, CAMILA; GAZZINELLI, RICARDO T.; ROMERO, OSCAR-BRUNA; LAZZARIN, MARIANA CRUZ; DOS SANTOS, JOSE FONTES; DE OLIVEIRA, FLAVIA; PISANI, LUCIANA PELLEGRINI; CARVALHO DE VASCONCELOS, JOSE RONNIE; RIBEIRO, DANIEL ARAKI. Therapeutic effects of vaccine derived from amastigote surface protein-2 (ASP-2) against Chagas disease in mouse liver. CYTOKINE, v. 113, p. 285-290, JAN 2019. Web of Science Citations: 1.
FERREIRA, CAMILA PONTES; CARISTE, LEONARDO MORO; VIRGILIO, FERNANDO DOS SANTOS; MORASCHI, BARBARA FERRI; MONTEIRO, CAROLINE BRANDAO; VIEIRA MACHADO, ALEXANDRE M.; GAZZINELLI, RICARDO TOSTES; BRUNA-ROMERO, OSCAR; MENIN RUIZ, PEDRO LUIZ; RIBEIRO, DANIEL ARAKI; LANNES-VIEIRA, JOSELI; LOPES, MARCELA DE FREITAS; RODRIGUES, MAURICIO MARTINS; CARVALHO DE VASCONCELOS, JOSE RONNIE. LFA-1 Mediates Cytotoxicity and Tissue Migration of Specific CD8(+) T Cells after Heterologous Prime-Boost Vaccination against Trypanosoma cruzi Infection. FRONTIERS IN IMMUNOLOGY, v. 8, OCT 13 2017. Web of Science Citations: 3.
EICKHOFF, CHRISTOPHER S.; ZHANG, XIULI; VASCONCELOS, JOSE R.; MOTZ, R. GEOFFREY; SULLIVAN, NICOLE L.; O'SHEA, KELLY; POZZI, NICOLA; GOHARA, DAVID W.; BLASE, JENNIFER R.; DI CERA, ENRICO; HOFT, DANIEL F. Costimulatory Effects of an Immunodominant Parasite Antigen Paradoxically Prevent Induction of Optimal CD8 T Cell Protective Immunity. PLOS PATHOGENS, v. 12, n. 9 SEP 2016. Web of Science Citations: 2.
ERSCHING, JONATAN; BASSO, ALEXANDRE SALGADO; GARCIA KALICH, VERA LUCIA; BORTOLUCI, KARINA RAMALHO; RODRIGUES, MAURICIO M. A Human Trypanosome Suppresses CD8(+) T Cell Priming by Dendritic Cells through the Induction of Immune Regulatory CD4(+) Foxp3(+) T Cells. PLOS PATHOGENS, v. 12, n. 6 JUN 2016. Web of Science Citations: 4.
ERSCHING, JONATAN; VASCONCELOS, JOSE R.; FERREIRA, CAMILA P.; CAETANO, BRAULIA C.; MACHADO, ALEXANDRE V.; BRUNA-ROMERO, OSCAR; BARON, MONIQUE A.; FERREIRA, LUDMILA R. P.; CUNHA-NETO, EDECIO; ROCK, KENNETH L.; GAZZINELLI, RICARDO T.; RODRIGUES, MAURCIO M. The Combined Deficiency of Immunoproteasome Subunits Affects Both the Magnitude and Quality of Pathogen- and Genetic Vaccination-Induced CD8(+) T Cell Responses to the Human Protozoan Parasite Trypanosoma cruzi. PLOS PATHOGENS, v. 12, n. 4 APR 2016. Web of Science Citations: 5.
VASCONCELOS, JOSE RONNIE; DOMINGUEZ, MARIANA R.; NEVES, RAMON L.; ERSCHING, JONATAN; ARAUJO, ADRIANO; SANTOS, LUARA I.; VIRGILIO, FERNANDO S.; MACHADO, ALEXANDRE V.; BRUNA-ROMERO, OSCAR; GAZZINELLI, RICARDO T.; RODRIGUES, MAURICIO M. Adenovirus Vector-Induced CD8(+) T Effector Memory Cell Differentiation and Recirculation, But Not Proliferation, Are Important for Protective Immunity Against Experimental Trypanosoma cruzi Infection. Human Gene Therapy, v. 25, n. 4, p. 350-363, APR 1 2014. Web of Science Citations: 10.
ARAUJO, ADRIANO FERNANDO; DE OLIVEIRA, GABRIEL; VASCONCELOS, JULIANA FRAGA; ERSCHING, JONATAN; DOMINGUEZ, MARIANA RIBEIRO; VASCONCELOS, JOSE RONNIE; MACHADO, ALEXANDRE VIEIRA; GAZZINELLI, RICARDO TOSTES; BRUNA-ROMERO, OSCAR; SOARES, MILENA BOTELHO; RODRIGUES, MAURICIO MARTINS. Genetic Vaccination against Experimental Infection with Myotropic Parasite Strains of Trypanosoma cruzi. Mediators of Inflammation, 2014. Web of Science Citations: 0.
VIRGILIO, FERNANDO DOS SANTOS; PONTES, CAMILA; DOMINGUEZ, MARIANA RIBEIRO; ERSCHING, JONATAN; RODRIGUES, MAURICIO MARTINS; VASCONCELOS, JOSE RONNIE. CD8(+) T Cell-Mediated Immunity during Trypanosoma cruzi Infection: A Path for Vaccine Development?. Mediators of Inflammation, 2014. Web of Science Citations: 12.

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