The role of mTOR in memory CD8 T-cell differentiation.
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 interferon. 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 among CD8(+) T cells, CD4(+) T cells, and dendritic cells. Also, we discuss potential application of these findings in a clinical setting.
Emory Vaccine Center and Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA 30322, USA.
Koichi
K
Araki
Ben
B
Youngblood
Rafi
R
Ahmed
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D002454:Cell Differentiation / Q000187:drug effects; D003713:Dendritic Cells / Q000276:immunology; D006801:Humans; D007155:Immunologic Factors / Q000494:pharmacology; D007156:Immunologic Memory / Q000187:drug effects; D047908:Intracellular Signaling Peptides and Proteins / Q000037:antagonists & inhibitors / Q000276:immunology*; D016377:Organ Transplantation; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000276:immunology*; D015398:Signal Transduction; D020123:Sirolimus / Q000494:pharmacology; D058570:TOR Serine-Threonine Kinases; D014612:Vaccines / Q000276:immunology; D014777:Virus Diseases / Q000276:immunology
D007155:Immunologic Factors; D047908:Intracellular Signaling Peptides and Proteins; D014612:Vaccines; C546842:MTOR protein, human; D017346:Protein Serine-Threonine Kinases; D058570:TOR Serine-Threonine Kinases; D020123:Sirolimus