EFFECT OF METABOLIC INHIBITORS ON CD8+ T CELL DIFFERENTIATION IN VITRO

• Grant number: 22/16013-3
• Support Opportunities: Scholarships in Brazil - Master
• Start date: July 01, 2023
• End date: March 31, 2025
• Field of knowledge: Biological Sciences - Immunology - Cellular Immunology
• Principal Investigator: João Gustavo Pessini Amarante Mendes
• Grantee: Michel Mouawad de Queiroz
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

The Immune System consists in a range of cellular and molecular mechanisms that promote host defense against pathogens and potentially harmful substances. The development of immune responses is required to be tightly regulated, since their defensive role needs to be accompanied by protective mechanisms for the organism. Presently, infections driven by intracellular pathogens and cancer represent the main causes of the death and became extremely relevant health care issues worldwide. CD8+ T lymphocytes play a crucial role in targeting and eliminating tumor cells and cells infected by intracellular pathogens, including viruses. During the differentiation process of activated CD8+ T cells into effector cells, distinct subsets can be generated depending on the polarization stimuli available in the microenvironment. Each subset presents a specific cytokine profile and distinct cytotoxic potential. Recently, many studies have established correlations between immune cells differentiation, effector activity and metabolism. Much is known about the metabolism of both naïve/resting and activated CD8+ T cells. However, there is a lack of information about metabolism during the differentiation process. In this context, the project will analyze the metabolic pathways used during polarization and by each effector subset. In this study, CD8+ T cells will be isolated from spleens of wild-type mice, activated and differentiated by specific polarizing cytokines. The metabolic profiles of activated and differentiated cells will be evaluated using specific metabolic inhibitors.