PMID- 21966447 OWN - NLM STAT- MEDLINE DCOM- 20120210 LR - 20211020 IS - 1932-6203 (Electronic) IS - 1932-6203 (Linking) VI - 6 IP - 9 DP - 2011 TI - Temporal regulation of rapamycin on memory CTL programming by IL-12. PG - e25177 LID - 10.1371/journal.pone.0025177 [doi] LID - e25177 AB - 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. FAU - Li, Xiangdong AU - Li X AD - Department of Animal and Avian Sciences, University of Maryland, College Park, Maryland, United States of America. FAU - Garcia, Karla AU - Garcia K FAU - Sun, Zhifeng AU - Sun Z FAU - Xiao, Zhengguo AU - Xiao Z LA - eng PT - Journal Article DEP - 20110923 PL - United States TA - PLoS One JT - PloS one JID - 101285081 RN - 126880-86-2 (L-Selectin) RN - 187348-17-0 (Interleukin-12) RN - W36ZG6FT64 (Sirolimus) SB - IM MH - Animals MH - Cells, Cultured MH - Flow Cytometry MH - Immunologic Memory/drug effects/immunology MH - Interleukin-12/*pharmacology MH - L-Selectin/metabolism MH - Mice MH - Reverse Transcriptase Polymerase Chain Reaction MH - Sirolimus/*pharmacology MH - T-Lymphocytes, Cytotoxic/*drug effects/*metabolism PMC - PMC3179471 COIS- Competing Interests: The authors have declared that no competing interests exist. EDAT- 2011/10/04 06:00 MHDA- 2012/02/11 06:00 PMCR- 2011/09/23 CRDT- 2011/10/04 06:00 PHST- 2011/06/24 00:00 [received] PHST- 2011/08/26 00:00 [accepted] PHST- 2011/10/04 06:00 [entrez] PHST- 2011/10/04 06:00 [pubmed] PHST- 2012/02/11 06:00 [medline] PHST- 2011/09/23 00:00 [pmc-release] AID - PONE-D-11-11704 [pii] AID - 10.1371/journal.pone.0025177 [doi] PST - ppublish SO - PLoS One. 2011;6(9):e25177. doi: 10.1371/journal.pone.0025177. Epub 2011 Sep 23.