title: Age-related changes in mature CD4+ T cells: cell cycle analysis.
abstract: T cell proliferative responses decrease with age, but the mechanisms responsible are unknown. We examined the impact of age on memory and naive CD4(+) T cell entry and progression through the cell cycle using acridine orange to identify cell cycle stage. For both subsets, fewer stimulated cells from old donors were able to enter and progress through the first cell cycle, with an increased number of cells arrested in G(0) and fewer cells in post G(0) phases. The number of dead cells as assessed by sub-G(0) DNA was also significantly greater in the old group. CD4(+) T cells from old mice also exhibited a significant reduction in clonal history as assessed by CFSE staining. This was associated with a significant decline in cyclin D2 mRNA and protein. We propose that decreases in cyclin D2 are at least partially responsible for the proliferative decline found in aged CD4(+) T cells.
authors.affiliation: Department of Epidemiology, University of Michigan, Ann Arbor, MI 48109-0940, USA.
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Hale
authors.forename: Bruce C
authors.initials: BC
authors.lastname: Richardson
authors.forename: Leonard I
authors.initials: LI
authors.lastname: Sweet
authors.forename: David L
authors.initials: DL
authors.lastname: McElligott
authors.forename: James E
authors.initials: JE
authors.lastname: Riggs
authors.forename: Elton B
authors.initials: EB
authors.lastname: Chu
authors.forename: Jacqueline M
authors.initials: JM
authors.lastname: Glynn
authors.forename: Dave
authors.initials: D
authors.lastname: LaFrenz
authors.forename: David N
authors.initials: DN
authors.lastname: Ernst
authors.forename: Rosemary
authors.initials: R
authors.lastname: Rochford
authors.forename: Monte V
authors.initials: MV
authors.lastname: Hobbs
mesh_terms: D000165:Acridine Orange / Q000032:analysis; D000375:Aging / Q000276:immunology*; D000818:Animals; D017252:CD3 Complex / Q000502:physiology; D015496:CD4-Positive T-Lymphocytes / Q000737:chemistry / Q000166:cytology*; D002453:Cell Cycle; D056742:Cyclin D2; D016213:Cyclins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D005456:Fluorescent Dyes / Q000032:analysis; D016193:G1 Phase / Q000502:physiology*; D005786:Gene Expression Regulation; D007156:Immunologic Memory; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D012333:RNA, Messenger / Q000032:analysis; D013047:Specific Pathogen-Free Organisms; D016176:T-Lymphocyte Subsets / Q000737:chemistry / Q000166:cytology
chemical_list: D017252:CD3 Complex; C486196:Ccnd2 protein, mouse; D056742:Cyclin D2; D016213:Cyclins; D005456:Fluorescent Dyes; D012333:RNA, Messenger; D000165:Acridine Orange