Emory University School of Medicine
ResearchTo develop a successful vaccine against pathogens such as HIV, HCV, malaria etc., it will be essential for the vaccine to induce not only neutralizing antibodies but also highly protective memory T cells that persist for a long time and quickly react once they encounter pathogens. These functional memory T cells are known to be generated after acute infections in which pathogens are cleared within 1~2 weeks. Thus, it is important to understand how functional memory T cells are induced from naïve T cells during acute infections. Recently, our study has uncovered that mTOR plays a critical role in memory CD8 T cell differentiation. mTOR is an evolutionally conserved serine/threonine kinase and regulates cell growth and proliferation. We found that inhibiting mTOR during CD8 T cell responses not only enhanced quantity of memory CD8 T cells but also improved quantity of them. Our study has implications that mTOR is a potential intracellular target to enhance vaccine-induced T cell memory. Our current efforts focus on understanding of molecular and cellular mechanisms by which mTOR pathways regulate memory CD8 T cell differentiation. We also study potential application of our findings in a clinical setting.
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2 Araki, K., Youngblood, B. and Ahmed, R., The role of mTOR in memory CD8 T-cell differentiation. Immunol Rev 2010. 235: 234-243.
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4 Araki, K., Ellebedy, A. H. and Ahmed, R., TOR in the immune system. Curr Opin Cell Biol 2011. 23: 707-715.
5 Araki, K. and Konieczny, B. T., Utilizing a retroviral RNAi system to investigate in vivo mTOR functions in T cells. Methods Mol Biol 2012. 821: 305-316.