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Regulation of FASL expression and CD4+ T lymphocytes survival by PGE2 during antigen presentation

Grant number: 10/00188-1
Support type:Scholarships in Brazil - Doctorate
Effective date (Start): July 01, 2010
Effective date (End): June 30, 2014
Field of knowledge:Biological Sciences - Immunology - Cellular Immunology
Principal researcher:João Gustavo Pessini Amarante Mendes
Grantee:Julia Cortina Campopiano
Home Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil


Antigen presenting cells (APCs) guide the responses of T lymphocytes through various mechanisms including the expression of costimulatory molecules and the cytokines and soluble factors production. These mechanisms influence not only in the proliferation, differentiation and polarization of T lymphocytes, but also interfere with the survival of these cells. Data published recently by our research group has demonstrated for the first time that PGE2 released by macrophages and dendritic cells in response to LPS, a TLR4 / MyD88 agonist, is able to exert a negative effect on the FasL induction mediated by stimulation TCR / CD3 complex. Added to this data, the results of my master's project demonstrate that soluble factors produced by macrophages derived from bone marrow and J774 strain stimulated with other TLR agonists (TLR1 / 2, TLR3, TLR4, TLR5, TLR7 and TLR9) can also inhibit FasL expression and consequently the AICD process. Importantly, our results were obtained with models that involve established T lymphocytes hybridoma and CD4 + T cells obtained from unimmunized mice and therefore probably naive T cells. In addition, we use an in vitro AICD protocol mimicked by using anti-CD3. In addition, we realize separate analysis of the supernatant of macrophages stimulated with TLR agonists T lymphocytes AICD. Protocol which has deficiency of the not share other macrophages co-stimulation. Therefore, this current project aims to expand the investigation of the results obtained in the Masters in a more complex and closer to the physiological level. In this sense, we discuss our hypothesis in models of antigen presentation, where APCs and T lymphocytes form a peculiar microenvironment. In these models, we will investigate the effect of TLR stimulation on CD4+ T lymphocytes FasL expression and therefore the potential for proliferation, activation, differentiation and survival of these APCs or lymphocytes.

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