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Master's Dissertation
DOI
https://doi.org/10.11606/D.42.2014.tde-14032015-101012
Document
Author
Full name
Pedro Henrique Papotto Rosa
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2014
Supervisor
Committee
Rizzo, Luiz Vicente (President)
Câmara, Niels Olsen Saraiva
Damico, Francisco Max
Title in Portuguese
Avaliação da eficiência do antagonista seletivo de CD28, mPEG PV1-Fab´, no tratamento da uveíte autoimune experimental.
Keywords in Portuguese
Bloqueio co-­estimulatório
CD28
EAU
IFN-­gamma
Th1
Uveíte
Abstract in Portuguese
A uveíte autoimune é uma doença inflamatória crônica, caracterizada pela resposta imune a antígenos oculares. É mediada por linfócitos T CD4+ com perfil TH1, e responsável por uma parcela significativa de casos de deficiências visuais e cegueira. Embora efetivos, os tratamentos disponíveis estão associados a efeitos adversos importantes. Logo, a busca de novos alvos terapêuticos mais específicos tem sido o objetivo principal no campo da imunoterapia. Nesse trabalho foi avaliada a eficiência do antagonista seletivo de CD28, mPEG PV1-Fab´(PV1), no tratamento da uveíte autoimune experimental (EAU). Camundongos tratados com PV1 exibiram menores graus de doença quando comparados a controles não tratados. Tal achado foi acompanhado de uma diminuição da ativação de linfócitos T, tanto nos olhos quanto nos órgãos linfoides periféricos desses animais. Mais ainda, o tratamento com PV1 levou a uma diminuição da população de linfócitos T reguladores e de células do tipo TH1. Portanto, concluiu-se que PV1 é eficaz no tratamento da EAU por agir em linfócitos T efetores.
Title in English
Efficacy of murine selective CD28 antagonist for the treatment of experimental autoimmune uveitis.
Keywords in English
CD28
Costimulatory blockade
EAU
IFN-­gamma
Th1
Uveitis
Abstract in English
Autoimmune uveitis is a T-cell mediated disease that targets mainly the posterior eye pole. Similar to human uveitis, experimental autoimmune uveitis (EAU) is mostly dependent on T cells with a TH1 phenotype. Although many treatment strategies are available, most of them focus on general immunossuppression, resulting in undesirable side effects. Thus, the development of more specific therapies is the major aim in the field of immunotherapy. Here we evaluated the efficacy of mPEG PV-1-Fab´ (PV1), a specific CD28 antagonist, in the treatment of EAU. Our results indicate that PV1 blocks T cell activation by decreasing expression of different costimulatory molecules. Furthermore, PV1 treatment led to a decrease of Treg cell population in peripheral lymphoid organs. Also, IFN-g production by CD4+ cells and TH1 lymphocytes population were decreased. Altogether, our results raise this CD28 blockade strategy as a potential tool for the treatment of autoimmune disorders in the eye, and indicate that mPEG PV1-Fab acts mainly on IFN-g production and TH1 polarization.
 
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Publishing Date
2015-03-14
 
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