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Age-related changes in mature CD4+ T cells: cell cycle analysis
Timothy J Hale1, Bruce C Richardson, Leonard I Sweet
1Department of Epidemiology, University of Michigan, Ann Arbor, MI 48109-0940, USA.
Cellular Immunology
|April 30, 2003
Summary
Aging impairs T cell proliferation due to reduced cell cycle entry and progression. Declines in cyclin D2 expression contribute to this age-related decrease in CD4(+) T cell function.
Area of Science:
- Immunology
- Cell Biology
- Gerontology
Background:
- T cell proliferative responses diminish with advancing age.
- The underlying mechanisms driving age-related decline in T cell function remain largely unknown.
Purpose of the Study:
- To investigate the impact of aging on the cell cycle entry and progression of memory and naive CD4(+) T cells.
- To identify molecular factors contributing to reduced T cell proliferation in older individuals.
Main Methods:
- Utilized acridine orange staining to assess cell cycle stages in CD4(+) T cells.
- Employed carboxyfluorescein succinimidyl ester (CFSE) staining to evaluate T cell clonal expansion.
- Quantified cyclin D2 mRNA and protein levels in T cells from young and old donors.
Main Results:
- Stimulated CD4(+) T cells from older donors showed reduced entry and progression through the cell cycle, with increased G(0) arrest.
- A higher proportion of dead cells (sub-G(0) DNA) was observed in T cells from aged individuals.
- A significant reduction in T cell clonal history and a decline in cyclin D2 expression were associated with aging.
Conclusions:
- Aging negatively affects CD4(+) T cell proliferation by hindering cell cycle progression and increasing cell death.
- Decreased expression of cyclin D2 is a key factor contributing to the impaired proliferative capacity of aged CD4(+) T cells.