Work

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

Year: 2010

Type: review

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 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.

Source: Immunological Reviews

DOI: 10.1111/j.0105-2896.2010.00898.x

Authors: Koichi Araki, Ben Youngblood, Rafi Ahmed

Institution: Emory University

Language: English

Topic: T-cell and B-cell Immunology

Subfield: Immunology

Field: Immunology and Microbiology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: green

Funders: American Cancer Society, Bill and Melinda Gates Foundation, National Institutes of Health, National Institute of Allergy and Infectious Diseases