title: Real-time tracking of cell cycle progression during CD8+ effector and memory T-cell differentiation.
abstract: The precise pathways of memory T-cell differentiation are incompletely understood. Here we exploit transgenic mice expressing fluorescent cell cycle indicators to longitudinally track the division dynamics of individual CD8(+) T cells. During influenza virus infection in vivo, naive T cells enter a CD62L(intermediate) state of fast proliferation, which continues for at least nine generations. At the peak of the anti-viral immune response, a subpopulation of these cells markedly reduces their cycling speed and acquires a CD62L(hi) central memory cell phenotype. Construction of T-cell family division trees in vitro reveals two patterns of proliferation dynamics. While cells initially divide rapidly with moderate stochastic variations of cycling times after each generation, a slow-cycling subpopulation displaying a CD62L(hi) memory phenotype appears after eight divisions. Phenotype and cell cycle duration are inherited by the progeny of slow cyclers. We propose that memory precursors cell-intrinsically modulate their proliferative activity to diversify differentiation pathways.
authors.affiliation: Immune Imaging Program, Centenary Institute for Cancer Medicine and Cell Biology, Newtown, New South Wales 2042, Australia.
authors.forename: Ichiko
authors.initials: I
authors.lastname: Kinjyo
authors.affiliation: Immune Imaging Program, Centenary Institute for Cancer Medicine and Cell Biology, Newtown, New South Wales 2042, Australia.
authors.forename: Jim
authors.initials: J
authors.lastname: Qin
authors.affiliation: Immune Imaging Program, Centenary Institute for Cancer Medicine and Cell Biology, Newtown, New South Wales 2042, Australia.
authors.forename: Sioh-Yang
authors.initials: SY
authors.lastname: Tan
authors.affiliation: 1] Division of Immunology, Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3052, Australia [2] Department of Medical Biology, University of Melbourne, Melbourne, Victoria 3052, Australia.
authors.forename: Cameron J
authors.initials: CJ
authors.lastname: Wellard
authors.affiliation: Immune Imaging Program, Centenary Institute for Cancer Medicine and Cell Biology, Newtown, New South Wales 2042, Australia.
authors.forename: Paulus
authors.initials: P
authors.lastname: Mrass
authors.affiliation: Immune Imaging Program, Centenary Institute for Cancer Medicine and Cell Biology, Newtown, New South Wales 2042, Australia.
authors.forename: William
authors.initials: W
authors.lastname: Ritchie
authors.affiliation: Cell Innovator Co., Ltd., Fukuoka 812-8581, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Doi
authors.affiliation: Immune Imaging Program, Centenary Institute for Cancer Medicine and Cell Biology, Newtown, New South Wales 2042, Australia.
authors.forename: Lois L
authors.initials: LL
authors.lastname: Cavanagh
authors.affiliation: Laboratory for Autoimmune Regulation, RIKEN Research Center for Allergy and Immunology, Yokohama 230-0045, Japan.
authors.forename: Michio
authors.initials: M
authors.lastname: Tomura
authors.affiliation: Laboratory for Cell Function and Dynamics, Brain Science Institute, RIKEN, Saitama 351-0198, Japan.
authors.forename: Asako
authors.initials: A
authors.lastname: Sakaue-Sawano
authors.affiliation: Laboratory for Autoimmune Regulation, RIKEN Research Center for Allergy and Immunology, Yokohama 230-0045, Japan.
authors.forename: Osami
authors.initials: O
authors.lastname: Kanagawa
authors.affiliation: Laboratory for Cell Function and Dynamics, Brain Science Institute, RIKEN, Saitama 351-0198, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Miyawaki
authors.affiliation: 1] Division of Immunology, Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3052, Australia [2] Department of Medical Biology, University of Melbourne, Melbourne, Victoria 3052, Australia.
authors.forename: Philip D
authors.initials: PD
authors.lastname: Hodgkin
authors.affiliation: 1] Immune Imaging Program, Centenary Institute for Cancer Medicine and Cell Biology, Newtown, New South Wales 2042, Australia [2] Discipline of Dermatology, Sydney Medical School, University of Sydney, Sydney, New South Wales 2006, Australia [3] Department of Dermatology, Royal Prince Alfred Hospital, Camperdown, New South Wales 2050, Australia.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Weninger
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology* / Q000502:physiology; D002453:Cell Cycle; D002454:Cell Differentiation; D020869:Gene Expression Profiling; D017930:Genes, Reporter; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D059467:Transcriptome