title: C-Myc regulation by costimulatory signals modulates the generation of CD8+ memory T cells during viral infection.
abstract: The signalling mechanisms of costimulation in the development of memory T cells remain to be clarified. Here, we show that the transcription factor c-Myc in CD8(+) T cells is controlled by costimulatory molecules, which modulates the development of memory CD8(+) T cells. C-Myc expression was dramatically reduced in Cd28(-/-) or Ox40(-/-) memory CD8(+) T cells, and c-Myc over-expression substantially reversed the defects in the development of T-cell memory following viral infection. C-Myc regulated the expression of survivin, an inhibitor of apoptosis, which promoted the generation of virus-specific memory CD8(+) T cells. Moreover, over-expression of survivin with bcl-xL, a downstream molecule of NF-κB and intracellular target of costimulation that controls survival, in Cd28(-/-) or Ox40(-/-) CD8(+) T cells, reversed the defects in the generation of memory T cells in response to viral infection. These results identify c-Myc as a key controller of memory CD8(+) T cells from costimulatory signals.
authors.affiliation: Department of Microbiology and Immunology, The Pennsylvania State University College of Medicine, Hershey, PA, USA.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Haque
authors.affiliation: Institutes of Irradiation/Immunology, The Third Military Medical University, Chongqing, People's Republic of China.
authors.forename: Jianyong
authors.initials: J
authors.lastname: Song
authors.affiliation: Department of Microbiology and Immunology, The Pennsylvania State University College of Medicine, Hershey, PA, USA.
authors.forename: Kristin
authors.initials: K
authors.lastname: Fino
authors.affiliation: Institutes of Irradiation/Immunology, The Third Military Medical University, Chongqing, People's Republic of China.
authors.forename: Youfei
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Microbiology and Immunology, The Pennsylvania State University College of Medicine, Hershey, PA, USA.
authors.forename: Praneet
authors.initials: P
authors.lastname: Sandhu
authors.affiliation: Department of Microbiology and Immunology, The Pennsylvania State University College of Medicine, Hershey, PA, USA.
authors.forename: Xinmeng
authors.initials: X
authors.lastname: Song
authors.affiliation: Department of Microbiology and Immunology, The Pennsylvania State University College of Medicine, Hershey, PA, USA.
authors.forename: Christopher
authors.initials: C
authors.lastname: Norbury
authors.affiliation: Institutes of Irradiation/Immunology, The Third Military Medical University, Chongqing, People's Republic of China.
authors.forename: Bing
authors.initials: B
authors.lastname: Ni
authors.affiliation: Department of Pathology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
authors.forename: Deyu
authors.initials: D
authors.lastname: Fang
authors.affiliation: Department of Pathology, Immunology and Laboratory Medicine, University of Florida, Gainesville, FL, USA.
authors.forename: Shahram
authors.initials: S
authors.lastname: Salek-Ardakani
authors.affiliation: Department of Microbiology and Immunology, The Pennsylvania State University College of Medicine, Hershey, PA, USA jus35@psu.edu.
authors.forename: Jianxun
authors.initials: J
authors.lastname: Song
mesh_terms: D000818:Animals; D018106:CD28 Antigens / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D005786:Gene Expression Regulation; D051550:I-kappa B Kinase / Q000378:metabolism; D007109:Immunity; D007156:Immunologic Memory / Q000235:genetics; D051034:Inhibitor of Apoptosis Proteins / Q000378:metabolism; D008822:Mice, Transgenic; D016328:NF-kappa B / Q000378:metabolism; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism*; D053262:Receptors, OX40; D012097:Repressor Proteins / Q000378:metabolism; D015398:Signal Transduction; D000077022:Survivin; D014158:Transcription, Genetic; D014777:Virus Diseases / Q000276:immunology*; D051020:bcl-X Protein / Q000378:metabolism
chemical_list: C117749:Birc5 protein, mouse; D018106:CD28 Antigens; D051034:Inhibitor of Apoptosis Proteins; D016328:NF-kappa B; D016271:Proto-Oncogene Proteins c-myc; D053262:Receptors, OX40; D012097:Repressor Proteins; D000077022:Survivin; C505717:Tnfrsf4 protein, mouse; D051020:bcl-X Protein; D051550:I-kappa B Kinase
keywords: CD8+ T cells; c-Myc; costimulation; memory; viral infection