Autophagy is an evolutionarily conserved process of cellular self-digestion, primarily used to maintain cellular energy homeostasis during starvation. In recent years, the new evidence is emerging implicating this process in development and differentiation, apoptosis, cancer, aging and senescence, and the immune response. In this proposal, we will utilize several strains of genetically modified mice to understand the role of autophagy in the T cell-mediated immune response. One group of mice will be used to study the induction of autophagic activity in different immune cells, such as lymphocytes, macrophages, and dendritic cells, under normal conditions and following immunization with an antigen by flow cytometry and biochemical assays. This group of mice contains several trangenic strains expressing green fluorescence protein-tagged versions of different autophagic proteins, such as Beclin 1, LC3, and Atg5. These reporter mice will allow us to determine a constitutive as well as antigen-induced autophagy in immune cells. To determine the function of autophagy in the T cell immune response, we will use mice deficient in autophagy essential protein Atg7. These mice will be immunized, and the T cell immune response to antigen in the absence of autophagy analyzed using flow cytometry and fuctional assays. This approach should provide a novel insight into the role of autophagy in the adaptive immune system.
In this proposal, we will characterize the role of autophagy in the adaptive immune system. This study should improve our understanding of the adaptive immunity, as well as of the role of autophagy in the initiation of the T cell immune activation and T cell memory, which are essential for the body's defense against different pathogens.
|Arsov, Ivica; Adebayo, Adeola; Kucerova-Levisohn, Martina et al. (2011) A role for autophagic protein beclin 1 early in lymphocyte development. J Immunol 186:2201-9|