title: MCL1 enhances the survival of CD8+ memory T Cells after viral infection.
abstract: Viral infection results in the generation of massive numbers of activated effector CD8(+) T cells that recognize viral components. Most of these are short-lived effector T cells (SLECs) that die after clearance of the virus. However, a small proportion of this population survives and forms antigen-specific memory precursor effector cells (MPECs), which ultimately develop into memory cells. These can participate in a recall response upon reexposure to antigen even at protracted times postinfection. Here, antiapoptotic myeloid cell leukemia 1 (MCL1) was found to prolong survival upon T cell stimulation, and mice expressing human MCL1 as a transgene exhibited a skewing in the proportion of CD8(+) T cells, away from SLECs toward MPECs, during the acute phase of vaccinia virus infection. A higher frequency and total number of antigen-specific CD8(+) T cells were observed in MCL1 transgenic mice. These findings show that MCL1 can shape the makeup of the CD8(+) T cell response, promoting the formation of long-term memory.
  
  
  OBJECTIVE
  During an immune response to a virus, CD8(+) T cells kill cells infected by the virus, and most die when the infection resolves. However, a small proportion of cells survives and differentiates into long-lived memory cells that confer protection from reinfection by the same virus. This report shows that transgenic expression of an MCL1 protein enhances survival of memory CD8(+) T cells following infection with vaccinia virus. This is important because it shows that MCL1 expression may be an important determinant of the formation of long-term CD8(+) T cell memory.
authors.affiliation: Department of Pharmacology and Toxicology, Geisel School of Medicine at Dartmouth, Hanover, New Hampshire, USA.
authors.forename: Jingang
authors.initials: J
authors.lastname: Gui
authors.affiliation: Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth, Lebanon, New Hampshire, USA.
authors.forename: Zhuting
authors.initials: Z
authors.lastname: Hu
authors.affiliation: Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth, Lebanon, New Hampshire, USA.
authors.forename: Ching-Yi
authors.initials: CY
authors.lastname: Tsai
authors.affiliation: Department of Pharmacology and Toxicology, Geisel School of Medicine at Dartmouth, Hanover, New Hampshire, USA.
authors.forename: Tian
authors.initials: T
authors.lastname: Ma
authors.affiliation: Department of Pharmacology and Toxicology, Geisel School of Medicine at Dartmouth, Hanover, New Hampshire, USA.
authors.forename: Yan
authors.initials: Y
authors.lastname: Song
authors.affiliation: Department of Pharmacology and Toxicology, Geisel School of Medicine at Dartmouth, Hanover, New Hampshire, USA.
authors.forename: Amanda
authors.initials: A
authors.lastname: Morales
authors.affiliation: Department of Biochemistry, Geisel School of Medicine at Dartmouth, Hanover, New Hampshire, USA.
authors.forename: Li-Hao
authors.initials: LH
authors.lastname: Huang
authors.affiliation: Department of Pharmacology and Toxicology, Geisel School of Medicine at Dartmouth, Hanover, New Hampshire, USA.
authors.forename: Ethan
authors.initials: E
authors.lastname: Dmitrovsky
authors.affiliation: Department of Pharmacology and Toxicology, Geisel School of Medicine at Dartmouth, Hanover, New Hampshire, USA edward.j.usherwood@dartmouth.edu ruth.w.craig@dartmouth.edu.
authors.forename: Ruth W
authors.initials: RW
authors.lastname: Craig
authors.affiliation: Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth, Lebanon, New Hampshire, USA edward.j.usherwood@dartmouth.edu ruth.w.craig@dartmouth.edu.
authors.forename: Edward J
authors.initials: EJ
authors.lastname: Usherwood
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000502:physiology*; D002470:Cell Survival; D004195:Disease Models, Animal; D006801:Humans; D007156:Immunologic Memory; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D064549:Myeloid Cell Leukemia Sequence 1 Protein / Q000235:genetics / Q000378:metabolism*; D014615:Vaccinia / Q000276:immunology*; D014616:Vaccinia virus / Q000276:immunology*
chemical_list: C579095:MCL1 protein, human; D064549:Myeloid Cell Leukemia Sequence 1 Protein