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

• Grant number: 12/22514-3
• Support Opportunities: Research Grants - Young Investigators Grants
• Start date: June 01, 2013
• End date: May 31, 2018
• Field of knowledge: Biological Sciences - Immunology - Cellular Immunology
• Principal Investigator: Jose Ronnie Carvalho de Vasconcelos
• Grantee: Jose Ronnie Carvalho de Vasconcelos
• Host Institution: Instituto de Saúde e Sociedade (ISS). Universidade Federal de São Paulo (UNIFESP). Campus Baixada Santista. Santos , SP, Brazil
• Associated researchers: Joseli Lannes Vieira ; Maurício Martins Rodrigues
• Associated research grant(s): 18/15607-1 - Role of specific CD4+ and CD8+ T cells generated by different vaccination protocols against experimental Trypanosoma cruzi infection, AP.JP2
• Associated scholarship(s): 17/11499-7 - Role of CX3CR1 chemokine receptor and the integrin LFA-1 in the differentiation and activation of CD8 + t lymphocytes during Trypanosoma cruzi infection, BP.MS; 15/08814-2 - Role of integrin receptors and chemokines in the migration of specific CD8+ T cells generated by genetic immunization with ASP -2 Trypanosoma cruzi, BP.DD; 15/24249-3 - Study of phenotype and specific CD8 + T cells function in immunized and/or infected mice by Trypanosoma cruzi after treatment with chemokine receptor blockers, BP.IC; 13/15794-2 - Role of receptor CXCR3, CCR2 and CCR5 in cell migration in specific CD8+ T cells after genetic immunization with the ASP-2 Trypanosoma cruzi, BP.MS; 13/10247-3 - Migration study of specific T cells generated by vaccination or Trypanosoma cruzi infection., BP.JP

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)

Scientific publications

(13)

(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)

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. (12/22514-3)

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. (12/13032-5, 09/06820-4, 12/22514-3)

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; et al. 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. (17/11499-7, 14/19422-5, 15/08814-2, 12/22514-3)

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; et al. Genetic Vaccination against Experimental Infection with Myotropic Parasite Strains of Trypanosoma cruzi. Mediators of Inflammation, v. 2014, p. 13-pg., 2014-01-01. (09/06820-4, 12/22514-3)

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, v. 2014, p. 12-pg., 2014-01-01. (13/13668-0, 09/06820-4, 12/22514-3)

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. (16/02840-4, 17/11499-7, 12/22514-3, 18/15607-1, 15/08814-2)

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; et al. 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. (12/22514-3)

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. (12/22514-3)

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; et al. Genetic Vaccination against Experimental Infection with Myotropic Parasite Strains of Trypanosoma cruzi. Mediators of Inflammation, 2014. (09/06820-4, 12/22514-3)

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. (13/13668-0, 09/06820-4, 12/22514-3)

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; et al. 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. (18/15607-1, 16/02840-4, 15/08814-2, 14/19422-5, 12/22514-3)

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.; et al. 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. (10/09361-8, 15/08814-2, 09/06820-4, 12/22514-3)

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.; et al. 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. (09/06820-4, 12/22514-3)