Age-related changes in mature CD4+ T cells: cell cycle analysis.
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.
Hale
Timothy J
TJ
Department of Epidemiology, University of Michigan, Ann Arbor, MI 48109-0940, USA.
Richardson
Bruce C
BC
Sweet
Leonard I
LI
McElligott
David L
DL
Riggs
James E
JE
Chu
Elton B
EB
Glynn
Jacqueline M
JM
LaFrenz
Dave
D
Ernst
David N
DN
Rochford
Rosemary
R
Hobbs
Monte V
MV
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
D017252:CD3 Complex; C486196:Ccnd2 protein, mouse; D056742:Cyclin D2; D016213:Cyclins; D005456:Fluorescent Dyes; D012333:RNA, Messenger; D000165:Acridine Orange