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

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Ferreira, Camila Pontes ^{[1, 2]} ; Cariste, Leonardo Moro ^{[3, 1]} ; Virgilio, Fernando Dos Santos ^{[1, 2]} ; Moraschi, Barbara Ferri ^{[1, 2]} ; Monteiro, Caroline Brandao ^[3] ; Vieira Machado, Alexandre M. ^[4] ; Gazzinelli, Ricardo Tostes ^{[4, 5]} ; Bruna-Romero, Oscar ^[6] ; Menin Ruiz, Pedro Luiz ^[3] ; Ribeiro, Daniel Araki ^[3] ; Lannes-Vieira, Joseli ^[7] ; Lopes, Marcela de Freitas ^[8] ; Rodrigues, Mauricio Martins ^{[1, 2]} ; Carvalho de Vasconcelos, Jose Ronnie ^{[3, 1, 2]}

Afiliação do(s) autor(es)

^[1] Ctr Mol & Cellular Therapy, Mol Immunol Lab, Sao Paulo - Brazil

^[2] Fed Univ Sao Paulo UNIFESP, Dept Microbiol Immunol & Parasitol, Sao Paulo - Brazil

^[3] Univ Fed Sao Paulo, Dept Biosci, Sao Paulo - Brazil

^[4] Fiocruz MS, Rene Rachou Res Ctr, Belo Horizonte, MG - Brazil

^[5] Univ Massachusetts, Sch Med, Dept Med, Div Infect Dis & Immunol, Worcester, MA - USA

^[6] Univ Fed Santa Catarina, Dept Microbiol Immunol & Parasitol, Florianopolis, SC - Brazil

^[7] Fiocruz MS, Oswaldo Cruz Inst, Biol Interact Lab, Rio De Janeiro - Brazil

^[8] Univ Fed Rio de Janeiro, Inst Biophys Carlos Chagas Filho, Rio De Janeiro - Brazil

• Tipo de documento: Artigo Científico
• Fonte: FRONTIERS IN IMMUNOLOGY; v. 8, OCT 13 2017.
• Citações Web of Science: 3

Resumo

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. (AU)

• Processo FAPESP: 17/11499-7 - Papel do receptor de quimiocinas CX3CR1 e da integrina LFA-1 na diferenciação e ativação de Linfócitos T CD8+ durante a infecção pelo Trypanosoma cruzi
• Beneficiário: Leonardo Moro Cariste
• Modalidade de apoio: Bolsas no Brasil - Mestrado
• Processo FAPESP: 14/19422-5 - Efeito do inibidor farmacológico de mTOR rapamicina na resposta de linfócitos T CD8+ de memória induzidos pela vacinação genética usando a estratégia de prime-boost heterólogo
• Beneficiário: Barbara Ferri Moraschi
• Modalidade de apoio: Bolsas no Brasil - Mestrado
• Processo FAPESP: 15/08814-2 - Papel de integrinas e receptores de quimiocinas na migração de células T CD8+ específicas geradas pela imunização genética com ASP-2 de Trypanosoma cruzi
• Beneficiário: Camila Pontes Ferreira
• Modalidade de apoio: Bolsas no Brasil - Doutorado Direto
• Processo FAPESP: 12/22514-3 - Estudo da migração de células T específicas geradas pela vacinação ou infecção pelo Trypanosoma cruzi
• Beneficiário: Jose Ronnie Carvalho de Vasconcelos
• Modalidade de apoio: Auxílio à Pesquisa - Jovens Pesquisadores