The role of mTOR in memory CD8+ T-cell differentiation

• Authors: Koichi Araki, Emory University; Benjamin Alan Youngblood, Emory University; Rafi Ahmed, Emory University
• Journal Title: Immunological Reviews
• Volume: Volume 235, Number 1
• Publisher: Wiley: 12 months | 2010-05, Pages 234-243
• Type of Work: Article | Post-print: After Peer Review
• Publisher DOI: http://doi.org/10.1111/j.0105-2896.2010.00898.x
• Subjects: Biology, Microbiology; Health Sciences, Immunology
• Keywords: mTOR; rapamycin; vaccination; infection; T cells; immune memory

Abstract

The mammalian target of rapamycin (mTOR) is an intracellular kinase that regulates cell growth and metabolism. Its specific inhibitor rapamycin is currently used in transplant recipients as an immunosuppressive drug to prevent allograft rejection. Studies have shown complex and diverse mechanisms for the immunosuppressive effects of rapamycin. The drug has been reported to inhibit T-cell proliferation, induce anergy, modulate T-cell trafficking, promote regulatory T cells, and also prevent maturation of dendritic cells as well as production of type I IFN production. However, several other studies have paradoxically demonstrated immunostimulatory effects of rapamycin by improving antigen presentation and regulating cytokine production from macrophages and myeloid dendritic cells. Recently, it has been shown that rapamycin also exhibits immunostimulatory effects on memory CD8+ T-cell differentiation. The drug improved both quantity and quality of memory CD8+ T cells induced by viral infection and vaccination, showing that mTOR is a major regulator of memory CD8+ T-cell differentiation. These discoveries have implications for the development of novel vaccine regimens. Here we review the role of mTOR in memory CD8+ T-cell differentiation and compare the effect of rapamycin between CD8+ T cells, CD4+ T cells, and dendritic cells. Also we discuss potential application of these findings in a clinical setting.