Cutting Edge: Generation of Effector Cells That Localize to Mucosal Tissues and Form Resident Memory CD8 T Cells Is Controlled by mTOR
- 1 September 2014
- journal article
- Published by The American Association of Immunologists in The Journal of Immunology
- Vol. 193 (5), 2067-2071
- https://doi.org/10.4049/jimmunol.1400074
Abstract
Mucosal tissues are subject to frequent pathogen exposure and are major sites for transmission of infectious disease. CD8 T cells play a critical role in controlling mucosa-acquired infections even though their migration into mucosal tissues is tightly regulated. The mechanisms and signals that control the formation of tissue-resident memory CD8 T cells are poorly understood; however, one key regulator of memory CD8 T cell differentiation, mammalian target of rapamycin kinase, can be inhibited by rapamycin. We report that, despite enhancing the formation of memory CD8 T cells in secondary lymphoid tissues, rapamycin inhibits the formation of resident memory CD8 T cells in the intestinal and vaginal mucosa. The ability of rapamycin to block the formation of functional resident CD8 T cells in mucosal tissues protected mice from a model of CD8 T cell–mediated lethal intestinal autoimmunity. These findings demonstrate an opposing role for mammalian target of rapamycin in the formation of resident versus nonresident CD8 T cell immunity.Keywords
This publication has 21 references indexed in Scilit:
- Antigen-Independent Differentiation and Maintenance of Effector-like Resident Memory T Cells in TissuesThe Journal of Immunology, 2012
- Regulating Mammalian Target of Rapamycin To Tune Vaccination-Induced CD8+ T Cell Responses for Tumor ImmunityPublished by The American Association of Immunologists ,2012
- TOR in the immune systemCurrent Opinion in Cell Biology, 2011
- Profound early control of highly pathogenic SIV by an effector memory T-cell vaccineNature, 2011
- Dynamic T cell migration program provides resident memory within intestinal epitheliumThe Journal of Experimental Medicine, 2010
- mTOR regulates memory CD8 T-cell differentiationNature, 2009
- Enhancing CD8 T-cell memory by modulating fatty acid metabolismNature, 2009
- Retinoic Acid Imprints Gut-Homing Specificity on T CellsImmunity, 2004
- Dynamics of Blood-Borne CD8 Memory T Cell Migration In VivoImmunity, 2004
- Preferential Localization of Effector Memory Cells in Nonlymphoid TissueScience, 2001