Temporal regulation of rapamycin on memory CTL programming by IL-12

Mammalian target of rapamycin (mTOR) is a master regulator of cell growth. Recent reports have defined its important role in memory cytotoxic T lymphocyte (CTL) differentiation in infections and memory programming. We report that rapamycin regulated memory CTL programming by IL-12 to a similar level...

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Bibliographic Details
Published in:PloS one 2011-09, Vol.6 (9), p.e25177-e25177
Main Authors: Li, Xiangdong, Garcia, Karla, Sun, Zhifeng, Xiao, Zhengguo
Format: Article
Language:English
Subjects:
Animals
B cells
Biology
Cell growth
Cells, Cultured
Cytotoxicity
Flow Cytometry
Health aspects
Immunologic Memory - drug effects
Immunologic Memory - immunology
Interleukin 12
Interleukin-12 - pharmacology
Kinases
L-selectin
L-Selectin - metabolism
Listeria
Listeria monocytogenes
Lymphocytes T
Medicine
Memory cells
Mice
Programming
Rapamycin
Reverse Transcriptase Polymerase Chain Reaction
Rodents
Sirolimus - pharmacology
T cell receptors
T cells
T-Lymphocytes, Cytotoxic - drug effects
T-Lymphocytes, Cytotoxic - metabolism
TOR protein
Veterinary Science
Viral infections
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Summary:Mammalian target of rapamycin (mTOR) is a master regulator of cell growth. Recent reports have defined its important role in memory cytotoxic T lymphocyte (CTL) differentiation in infections and memory programming. We report that rapamycin regulated memory CTL programming by IL-12 to a similar level in a wide range of concentrations, and the enhanced memory CTLs by rapamycin were functional and provided similar protection against Listeria Monocytogenes challenge compared to the control. In addition, rapamycin-experienced CTLs went through substantially enhanced proliferation after transfer into recipients. Furthermore, the regulatory function of rapamycin on CD62L expression in memory CTLs was mainly contributed by the presence of rapamycin in the first 24-hr of stimulation in vitro, whereas the effective window of rapamycin on the size of memory CTLs was determined between 24 to 72 hrs. In conclusion, rapamycin regulates IL-12-driven programming of CTLs to a similar level in a wide range of concentrations, and regulates the phenotype and the size of memory CTLs in different temporal windows.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0025177