title: T-cell stimuli independently sum to regulate an inherited clonal division fate.
abstract: In the presence of antigen and costimulation, T cells undergo a characteristic response of expansion, cessation and contraction. Previous studies have revealed that population-level reproducibility is a consequence of multiple clones exhibiting considerable disparity in burst size, highlighting the requirement for single-cell information in understanding T-cell fate regulation. Here we show that individual T-cell clones resulting from controlled stimulation in vitro are strongly lineage imprinted with highly correlated expansion fates. Progeny from clonal families cease dividing in the same or adjacent generations, with inter-clonal variation producing burst-size diversity. The effects of costimulatory signals on individual clones sum together with stochastic independence; therefore, the net effect across multiple clones produces consistent, but heterogeneous population responses. These data demonstrate that substantial clonal heterogeneity arises through differences in experience of clonal progenitors, either through stochastic antigen interaction or by differences in initial receptor sensitivities.
authors.affiliation: Division of Immunology, The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, Victoria 3052, Australia.|Department of Medical Biology, The University of Melbourne, Parkville, Victoria 3010, Australia.
authors.forename: J M
authors.initials: JM
authors.lastname: Marchingo
authors.affiliation: Hamilton Institute, Maynooth University, Maynooth, Co Kildare W23 WK26, Ireland.
authors.forename: G
authors.initials: G
authors.lastname: Prevedello
authors.affiliation: Division of Immunology, The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, Victoria 3052, Australia.|Department of Medical Biology, The University of Melbourne, Parkville, Victoria 3010, Australia.
authors.forename: A
authors.initials: A
authors.lastname: Kan
authors.affiliation: Division of Immunology, The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, Victoria 3052, Australia.|Department of Medical Biology, The University of Melbourne, Parkville, Victoria 3010, Australia.
authors.forename: S
authors.identifier: 0000-0001-9524-2835
authors.initials: S
authors.lastname: Heinzel
authors.affiliation: Division of Immunology, The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, Victoria 3052, Australia.|Department of Medical Biology, The University of Melbourne, Parkville, Victoria 3010, Australia.
authors.forename: P D
authors.initials: PD
authors.lastname: Hodgkin
authors.affiliation: Hamilton Institute, Maynooth University, Maynooth, Co Kildare W23 WK26, Ireland.
authors.forename: K R
authors.initials: KR
authors.lastname: Duffy
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000502:physiology*; D002455:Cell Division / Q000502:physiology; D049109:Cell Proliferation; D002478:Cells, Cultured; D002999:Clone Cells; D005456:Fluorescent Dyes; D057166:High-Throughput Screening Assays; D051379:Mice; D008815:Mice, Inbred Strains
chemical_list: D005456:Fluorescent Dyes