Investigating of the relationship between the modulation of FASL expression by PGE2 and CD4+ T lymphocytes survival

• Grant number: 11/06177-4
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: October 01, 2011
• End date: September 30, 2015
• Field of knowledge: Biological Sciences - Immunology - Cellular Immunology
• Principal Investigator: João Gustavo Pessini Amarante Mendes
• Grantee: Luciana Paroneto Medina
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

CD4+ T lymphocytes (LTCD4+) play a central role in immune response, due to their capability of controlling the action of other cell types through different signals, increasing their performance and allowing establishment of a more effective immune response. During lymphocytes development, a constant balance between proliferation and cell death, such as apoptosis, is important. When a significant reduction of LTCD4 death occurs, it can result in lymphoaccumulation and development of autoimmune diseases, whereas the exacerbation of apoptotic signals observed in syndromes, such as AIDS (Acquired Immune Deficiency Syndrome), leads to an immunodeficient state that makes the individual susceptible to many opportunistic infections. Previous data obtained by our research group (Weinlich et al., 2008) showed that it is possible to modulate the survival of CD4 T lymphocytes. When certain APCs (antigen presenting cells) were stimulated by LPS (Lipopolysaccharide) through TLR4 (toll-like receptor 4) via MyD88 (myeloid differentiation primary response gene 88) were released various soluble factors able to protect T lymphocytes from AICD (activation induced cell death). Based on this data, our working hypothesis is that it is possible to modulate CD4+ T cells survival in different pathophysiological conditions by modulating the levels of FASL by treatment with PGE2 or indomethacin, a non-steroidal anti-inflammatory able to block the activity of the cyclooxygenase enzyme and prevent the formation of prostaglandins. For this, we will perform the treatment of cultures of CD4 T lymphocytes, infected by HIV, with PGE2 and check if it is possible to reduce the levels of FASL prolonging the lymphocytes survival. On the other hand, we will induce EAE (Experimental Autoimmune encephalomyelitis) in mice and treat them with indomethacin and observe if there is an increase of FASL and decreased lymphocytes survival. Finally, we will evaluate the effect of administration of PGE2 and indomethacin in recently immunized mice and verify if there is any change in CD4 T cells proliferation and/or death.

Academic Publications

(References retrieved automatically from State of São Paulo Research Institutions)

MEDINA, Luciana Paroneto. Modulation of FASL expression by PGE2 and CD4+ T lymphocyte survival.. 2015. Doctoral Thesis - Universidade de São Paulo (USP). Instituto de Ciências Biomédicas (ICB/SDI) São Paulo.