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The effect of aging and caloric restriction on murine CD8+ T cell chemokine receptor gene expression.

Yung R, Mo R, Grolleau-Julius A, Hoeltzel M - Immun Ageing (2007)

Bottom Line: In this study we have examined the effect of aging on murine CD8+ T cell chemokine receptor gene expression.These findings are consistent with the notion that aging exists in a state of low grade pro-inflammatory environment.In addition, our results provide a potential mechanism for the reported aging-associated impaired T cell lymphoid homing and allograft response, and reduced survival in sepsis.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA. ryung@umich.edu

ABSTRACT

Background: The mechanism explaining the increased disease susceptibility in aging is not well understood. CD8+ T cells are crucial in anti-viral and anti-tumor responses. Although the chemokine system plays a critical role in CD8+ T cell function, very little is known about the relationship between aging and the T cell chemokine system.

Results: In this study we have examined the effect of aging on murine CD8+ T cell chemokine receptor gene expression. Freshly isolated splenic CD8+ T cells from old C57BL/6 mice were found to have higher CCR1, CCR2, CCR4, CCR5 and CXCR5, and lower CCR7 gene expression compared to their younger cohort. Anti-CD3/anti-CD28 stimulation elicited a similar robust chemokine receptor response from young and old CD8+ T cells. Western blot analyses confirmed elevated protein level of CCR4 and CCR5 in aged CD8+ T cells. Increases in T cell CCR1 and CCR5 expression also correlate to increased in vitro chemotaxis response to macrophage-inflammatory protein-1 alpha(MIP-1alpha). Finally, caloric restriction selectively prevents the loss of CD8+ T cell CCR7 gene expression in aging to the level that is seen in young CD8+ T cells.

Conclusion: These findings are consistent with the notion that aging exists in a state of low grade pro-inflammatory environment. In addition, our results provide a potential mechanism for the reported aging-associated impaired T cell lymphoid homing and allograft response, and reduced survival in sepsis.

No MeSH data available.


Related in: MedlinePlus

Effect of aging on murine CD8+ T cell chemotaxis response to MIP-1α. The indicated concentrations of the chemokine were placed in the lower chamber of a Costar Transwell system. Equal number of freshly isolated young (3–4 months) or old (18–20 months) CD8+ T cells was then placed in the upper chamber of the insert, and the number of cells in the upper and lower chambers counted 5 hours later using a Coulter counter. The results are expressed as percent transmigration and represent the mean ± SD of triplicate determinations. P ≤ 0.05 is considered significant. The results are representative of 3 independent experiments.
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Figure 5: Effect of aging on murine CD8+ T cell chemotaxis response to MIP-1α. The indicated concentrations of the chemokine were placed in the lower chamber of a Costar Transwell system. Equal number of freshly isolated young (3–4 months) or old (18–20 months) CD8+ T cells was then placed in the upper chamber of the insert, and the number of cells in the upper and lower chambers counted 5 hours later using a Coulter counter. The results are expressed as percent transmigration and represent the mean ± SD of triplicate determinations. P ≤ 0.05 is considered significant. The results are representative of 3 independent experiments.

Mentions: To determine if increased chemokine receptor gene expression correlates to increase CD8+ T cell chemotaxis function, we compared the in vitro migration response of young and old CD8+ T cells to MIP-1α (Figure 5), a ligand for CCR1 and CCR5. The results showed increased migration of old CD8+ T cells to the chemokine, confirming functional significance of the increased CCR1 and 5 expressions in old CD8+ T cells.


The effect of aging and caloric restriction on murine CD8+ T cell chemokine receptor gene expression.

Yung R, Mo R, Grolleau-Julius A, Hoeltzel M - Immun Ageing (2007)

Effect of aging on murine CD8+ T cell chemotaxis response to MIP-1α. The indicated concentrations of the chemokine were placed in the lower chamber of a Costar Transwell system. Equal number of freshly isolated young (3–4 months) or old (18–20 months) CD8+ T cells was then placed in the upper chamber of the insert, and the number of cells in the upper and lower chambers counted 5 hours later using a Coulter counter. The results are expressed as percent transmigration and represent the mean ± SD of triplicate determinations. P ≤ 0.05 is considered significant. The results are representative of 3 independent experiments.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2200663&req=5

Figure 5: Effect of aging on murine CD8+ T cell chemotaxis response to MIP-1α. The indicated concentrations of the chemokine were placed in the lower chamber of a Costar Transwell system. Equal number of freshly isolated young (3–4 months) or old (18–20 months) CD8+ T cells was then placed in the upper chamber of the insert, and the number of cells in the upper and lower chambers counted 5 hours later using a Coulter counter. The results are expressed as percent transmigration and represent the mean ± SD of triplicate determinations. P ≤ 0.05 is considered significant. The results are representative of 3 independent experiments.
Mentions: To determine if increased chemokine receptor gene expression correlates to increase CD8+ T cell chemotaxis function, we compared the in vitro migration response of young and old CD8+ T cells to MIP-1α (Figure 5), a ligand for CCR1 and CCR5. The results showed increased migration of old CD8+ T cells to the chemokine, confirming functional significance of the increased CCR1 and 5 expressions in old CD8+ T cells.

Bottom Line: In this study we have examined the effect of aging on murine CD8+ T cell chemokine receptor gene expression.These findings are consistent with the notion that aging exists in a state of low grade pro-inflammatory environment.In addition, our results provide a potential mechanism for the reported aging-associated impaired T cell lymphoid homing and allograft response, and reduced survival in sepsis.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA. ryung@umich.edu

ABSTRACT

Background: The mechanism explaining the increased disease susceptibility in aging is not well understood. CD8+ T cells are crucial in anti-viral and anti-tumor responses. Although the chemokine system plays a critical role in CD8+ T cell function, very little is known about the relationship between aging and the T cell chemokine system.

Results: In this study we have examined the effect of aging on murine CD8+ T cell chemokine receptor gene expression. Freshly isolated splenic CD8+ T cells from old C57BL/6 mice were found to have higher CCR1, CCR2, CCR4, CCR5 and CXCR5, and lower CCR7 gene expression compared to their younger cohort. Anti-CD3/anti-CD28 stimulation elicited a similar robust chemokine receptor response from young and old CD8+ T cells. Western blot analyses confirmed elevated protein level of CCR4 and CCR5 in aged CD8+ T cells. Increases in T cell CCR1 and CCR5 expression also correlate to increased in vitro chemotaxis response to macrophage-inflammatory protein-1 alpha(MIP-1alpha). Finally, caloric restriction selectively prevents the loss of CD8+ T cell CCR7 gene expression in aging to the level that is seen in young CD8+ T cells.

Conclusion: These findings are consistent with the notion that aging exists in a state of low grade pro-inflammatory environment. In addition, our results provide a potential mechanism for the reported aging-associated impaired T cell lymphoid homing and allograft response, and reduced survival in sepsis.

No MeSH data available.


Related in: MedlinePlus