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Doctoral Thesis
Full name
Julia Cortina Campopiano
Knowledge Area
Date of Defense
São Paulo, 2014
Mendes, Joao Gustavo Pessini Amarante (President)
Peron, Jean Pierre Schatzmann
Steiner, Alexandre Alarcon
Victor, Jefferson Russo
Viola, João Paulo de Biaso
Title in Portuguese
Regulação da expressão de FASL e sobrevivência dos linfócitos T CD4+ pela PGE2 durante a apresentação antigênica.
Keywords in Portuguese
Apresentação antigênica
Morte celular
Abstract in Portuguese
Após a resposta imune, a expansão dos linfócitos T CD4 é seguida de uma fase de retração chamada Morte Celular induzida por Ativação (AICD), para que a homeostasia seja reestabelecida. Nosso grupo demonstrou que DCs estimuladas com LPS produzem PGE2 que inibe a expressão de FASL e bloqueia a AICD dos linfócitos T CD4. Nossa hipótese é que a apresentação de antígenos em contexto de infecção tenha um impacto na expressão de FASL e na sobrevivência das células T CD4, de maneira dependente de TLRPGE2. Para comprovar nossa hipótese nós estudamos a apresentação de OVA in vitro e in vivo. Observamos que a adição de LPS durante a apresentação de OVA aumenta a ativação e proliferação das células T CD4 específicas. O pré-tratamento dos camundongos com Indometacina, um inibidor da enzima COX, reduz a frequência das células específicas através do aumento na expressão de FASL e da apoptose, mas sem interferir com a proliferação. Nós sugerimos que a PGE2 produzida em resposta ao LPS regule a sobrevivência dos linfócitos T CD4 durante a persistência do estímulo antigênico.
Title in English
Regulation of FASL expression and CD4+ T lymphocytes survival by PGE2 during antigen presentation.
Keywords in English
Antigen presentation
Cell death
Abstract in English
After immune response, expansion of antigen-specific CD4 T cells is followed by a contraction phase due to Activation-Induced Cell Death (AICD) to reestablish homeostasis. Our group demonstrated that LPS stimulated-DCs produce PGE2 that protects CD4 T cells from AICD by preventing TCR/CD3-mediated FASL upregulation. Our hypothesis is that antigen presentation in the context of infection impacts on FASL expression and survival of CD4 T cells, dependently on TLR-mediated PGE2 release. To approach our hypothesis we studied OVA presentation in vitro and in vivo. We observed that the addition of LPS during OVA presentation increased specific CD4+ T cells activation and proliferation. Pretreatment of mice with indomethacin, an inhibitor of COX enzyme, reduces the frequency of specific T cells by increasing FASL expression and apoptosis, but did not interfere with proliferation. We suggest that PGE2 produced in response to LPS regulates the survival of CD4 T lymphocytes during persistent antigen stimulation.
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  • Buzzo, C. L., et al. A novel pathway for inducible nitric oxide synthase (iNOS) activation through inflammasomes [doi:10.1074/jbc.M110.124297]. The Journal of Biological Chemistry [online], 2010, vol. 285, p. 32087-32095.
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