LFA-1 Mediates Cytotoxicity and Tissue Migration of Specific CD8(+) T Cells after Heterologous Prime-Boost Vaccination against Trypanosoma cruzi Infection

LFA-1 Mediates Cytotoxicity and Tissue Migration of Specific CD8(+) T Cells after Heterologous Prime-Boost Vaccination against Trypanosoma cruzi Infection

Author Ferreira, Camila Pontes Autor UNIFESP Google Scholar
Cariste, Leonardo Moro Autor UNIFESP Google Scholar
Virgilio, Fernando Dos Santos Autor UNIFESP Google Scholar
Moraschi, Barbara Ferri Autor UNIFESP Google Scholar
Monteiro, Caroline Brandao Autor UNIFESP Google Scholar
Vieira Machado, Alexandre M. Google Scholar
Gazzinelli, Ricardo Tostes Google Scholar
Bruna-Romero, Oscar Google Scholar
Menin Ruiz, Pedro Luiz Autor UNIFESP Google Scholar
Ribeiro, Daniel Araki Autor UNIFESP Google Scholar
Lannes-Vieira, Joseli Google Scholar
Lopes, Marcela de Freitas Google Scholar
Rodrigues, Mauricio Martins Autor UNIFESP Google Scholar
Carvalho de Vasconcelos, Jose Ronnie Autor UNIFESP Google Scholar
Abstract Integrins mediate the lymphocyte migration into an infected tissue, and these cells are essential for controlling the multiplication of many intracellular parasites such as Trypanosoma cruzi, the causative agent of Chagas disease. Here, we explore LFA-1 and VLA-4 roles in the migration of specific CD8(+) T cells generated by heterologous prime-boost immunization during experimental infection with T. cruzi. To this end, vaccinated mice were treated with monoclonal anti-LFA-1 and/or anti-VLA-4 to block these molecules. After anti-LFA-1, but not anti-VLA-4 treatment, all vaccinated mice displayed increased blood and tissue parasitemia, and quickly succumbed to infection. In addition, there was an accumulation of specific CD8(+) T cells in the spleen and lymph nodes and a decrease in the number of those cells, especially in the heart, suggesting that LFA-1 is important for the output of specific CD8(+) T cells from secondary lymphoid organs into infected organs such as the heart. The treatment did not alter CD8(+) T cell effector functions such as the production of pro-inflammatory cytokines and granzyme B, and maintained the proliferative capacity after treatment. However, the specific CD8(+) T cell direct cytotoxicity was impaired after LFA-1 blockade. Also, these cells expressed higher levels of Fas/CD95 on the surface, suggesting that they are susceptible to programmed cell death by the extrinsic pathway. We conclude that LFA-1 plays an important role in the migration of specific CD8(+) T cells and in the direct cytotoxicity of these cells.
Keywords vaccination
Trypanosoma cruzi
migration
integrins
specific CD8(+) T cells
xmlui.dri2xhtml.METS-1.0.item-coverage Lausanne
Language English
Sponsor Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP)
FAPESP
CNPq
Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES)
UFRJ
US National Institutes of Health (NIAID)
Grant number FAPESP: 2012/22514-3
FAPESP: 2015/08814-2
FAPESP: 2017/11499-7
FAPESP: 2014/19422-5
Date 2017
Published in Frontiers In Immunology. Lausanne, v. 8, p. -, 2017.
ISSN 1664-3224 (Sherpa/Romeo, impact factor)
Publisher Frontiers Media Sa
Extent -
Origin http://dx.doi.org/10.3389/fimmu.2017.01291
Access rights Open access Open Access
Type Article
Web of Science ID WOS:000412868400001
URI https://repositorio.unifesp.br/handle/11600/57150

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