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Efficacy of murine selective CD28 antagonist for the treatment of experimental autoimmune uveitis.

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Pedro Henrique Papotto Rosa
Total Authors: 1
Document type: Master's Dissertation
Press: São Paulo.
Institution: Universidade de São Paulo (USP). Instituto de Ciências Biomédicas (ICB/SDI)
Defense date:
Examining board members:
Luiz Vicente Rizzo; Niels Olsen Saraiva Câmara; Francisco Max Damico
Advisor: Luiz Vicente Rizzo

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. (AU)

FAPESP's process: 13/15448-7 - Efficacy evaluation of murine selective CD28 antagonist, mPEG PV1-Fab', for the treatment of experimental autoimmune uveitis
Grantee:Pedro Henrique Papotto Rosa
Support Opportunities: Scholarships in Brazil - Master