title: Temporal regulation of rapamycin on memory CTL programming by IL-12.
abstract: 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.
authors.affiliation: Department of Animal and Avian Sciences, University of Maryland, College Park, Maryland, United States of America.
authors.forename: Xiangdong
authors.initials: X
authors.lastname: Li
authors.forename: Karla
authors.initials: K
authors.lastname: Garcia
authors.forename: Zhifeng
authors.initials: Z
authors.lastname: Sun
authors.forename: Zhengguo
authors.initials: Z
authors.lastname: Xiao
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D005434:Flow Cytometry; D007156:Immunologic Memory / Q000187:drug effects / Q000276:immunology; D018664:Interleukin-12 / Q000494:pharmacology*; D019041:L-Selectin / Q000378:metabolism; D051379:Mice; D020133:Reverse Transcriptase Polymerase Chain Reaction; D020123:Sirolimus / Q000494:pharmacology*; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects* / Q000378:metabolism*
chemical_list: D019041:L-Selectin; D018664:Interleukin-12; D020123:Sirolimus