Papel do CXCR3 e LFA-1 na migração e função dos linfócitos T CD8+ induzidos pela imunização com ASP-2 e infecção pelo Trypanosoma cruzi

• Autor(a) principal: Ferreira, Camila Pontes [UNIFESP]
• Data de Publicação: 2019
• Tipo de documento: Tese
• Idioma: por
• Título da fonte: Repositório Institucional da UNIFESP
• Texto Completo: https://sucupira.capes.gov.br/sucupira/public/consultas/coleta/trabalhoConclusao/viewTrabalhoConclusao.jsf?popup=true&id_trabalho=8038905; https://repositorio.unifesp.br/handle/11600/59389
• topic: CD8+ T lymphocytes; LFA-1; CXCR3; Trypanosoma cruzi; Linfócitos T CD8+; LFA-1; CXCR3; Trypanosoma cruzi

Chagas disease remains a serious health problem in the Latin America. Trypanosoma cruzi is the causative agent of this disease and it is able to activate the innate immune system; however, the most important cells that control the infection by T. cruzi are CD8+ T lymphocytes. Those cells recognize epitopes from trypomastigote and amastigote forms of T. cruzi, that are presented by antigen presenting cells via MHCI. Despite their importance in the T. cruzi infection, CD8+ T lymphocytes fail to induce a sterile infection, and the persistence of the parasite in the host characterize the chronic phase of the disease. Several studies report that the establishment of that phase is caused by the delay of CD8+ T cells appearance. In order to accelerate CD8+ T cells appearance, our group developed a heterologous prime-boost vaccination strategy, using a DNA plasmid as the prime, followed by the boost with human adenovirus type 5, both carrying the surface protein 2 gene of T. cruzi. That protocol accelerates the induction of CD8+ T lymphocytes and decreases the pro-apoptotic profile of those cells, generating a pool of memory lymphocyte able to protect highly susceptible mice against T. cruzi infection. The protection induced by the heterologous prime-boost immunization was dependent on the recirculation of CD8+ T lymphocytes. Thus, this study aimed to investigate integrin and chemokine molecules, that are responsible for cell migration during homeostasis and inflammation. Th1 chemokines, CXCR3 and LFA-1 integrin, were the main molecules evaluated, both highly expressed in T lymphocytes during T. cruzi infection. We observed that both molecules are fundamental for the migration of CD8+ T lymphocytes to the heart of infected animals. In addition, these molecules were important in the cytotoxicity of CD8+ T lymphocytes. Regarding CXCR3, it was fundamental for migration of plasmacytoid dendritic cells and CD8+ T cells activation. Given the important role of these molecules in the migration and functionality of CD8+ T lymphocytes, their use in vaccine strategies against T. cruzi infection are promising.