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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

The effect of caloric restriction on CD8+ T cell chemokine receptor expression in aging. Ribonuclease protection assays (RPAs) were done using RNA from freshly isolated splenic CD8+ T cells from young (3–4 months), old (18–20 months), and caloric restricted old (18–20 months) mice in groups of 5 animals. Density of the bands was quantified using a phosphoimager. (A) Histogram showing the composite data of 4 experiments (total 20 animals in each condition). The results represent the mean ± SEM of the relative CD8+ T cell chemokine receptor gene expression level of old and old caloric restricted mice compared to those from the young cohort (arbitrarily defined as equal to 1). (B) CCR7 expression was also determined using a custom CCR7 RPA probe. The left panel is a representative autoradiograph (lane 1 = young CD8+ T cells; lane 2 = old CD8+ T cells; lane 3 = caloric restricted old CD8+ T cells). The right panel represents the composite data of 3 RPAs with a total of 15 animals in each group. Results are presented as mean ± SEM. CR = caloric restricted. Gel loading is corrected with L32 expression.
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Figure 3: The effect of caloric restriction on CD8+ T cell chemokine receptor expression in aging. Ribonuclease protection assays (RPAs) were done using RNA from freshly isolated splenic CD8+ T cells from young (3–4 months), old (18–20 months), and caloric restricted old (18–20 months) mice in groups of 5 animals. Density of the bands was quantified using a phosphoimager. (A) Histogram showing the composite data of 4 experiments (total 20 animals in each condition). The results represent the mean ± SEM of the relative CD8+ T cell chemokine receptor gene expression level of old and old caloric restricted mice compared to those from the young cohort (arbitrarily defined as equal to 1). (B) CCR7 expression was also determined using a custom CCR7 RPA probe. The left panel is a representative autoradiograph (lane 1 = young CD8+ T cells; lane 2 = old CD8+ T cells; lane 3 = caloric restricted old CD8+ T cells). The right panel represents the composite data of 3 RPAs with a total of 15 animals in each group. Results are presented as mean ± SEM. CR = caloric restricted. Gel loading is corrected with L32 expression.

Mentions: Caloric restriction has been shown to prolong life in mice and to restore many of the aging-associated defects in T cell immune functions [26]. In addition, caloric restriction may affect CD4+ T cell chemokine receptor gene expression in aging [21]. In the current study we did not see any significant effect of caloric restriction on CD8+ T cell chemokine receptor expression compared to ad lib fed mice (Figure 3A). Although the CD8+ T cell CCR1, CCR3 and CXCR4 expression in caloric restricted mice approximates that seen in the young mice, the results did not reach statistical significance. We also examined the effect of caloric restriction on CCR7 expression using a custom RPA probe set as before [21]. The results show reduced CCR7 expression in old CD8+ T cells, similar to that reported in CD4+ T cells in aging [21,27]. Interestingly, caloric restriction selectively prevents the loss of CCR7 expression in CD8+ T cells (Figure 3B).


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)

The effect of caloric restriction on CD8+ T cell chemokine receptor expression in aging. Ribonuclease protection assays (RPAs) were done using RNA from freshly isolated splenic CD8+ T cells from young (3–4 months), old (18–20 months), and caloric restricted old (18–20 months) mice in groups of 5 animals. Density of the bands was quantified using a phosphoimager. (A) Histogram showing the composite data of 4 experiments (total 20 animals in each condition). The results represent the mean ± SEM of the relative CD8+ T cell chemokine receptor gene expression level of old and old caloric restricted mice compared to those from the young cohort (arbitrarily defined as equal to 1). (B) CCR7 expression was also determined using a custom CCR7 RPA probe. The left panel is a representative autoradiograph (lane 1 = young CD8+ T cells; lane 2 = old CD8+ T cells; lane 3 = caloric restricted old CD8+ T cells). The right panel represents the composite data of 3 RPAs with a total of 15 animals in each group. Results are presented as mean ± SEM. CR = caloric restricted. Gel loading is corrected with L32 expression.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 3: The effect of caloric restriction on CD8+ T cell chemokine receptor expression in aging. Ribonuclease protection assays (RPAs) were done using RNA from freshly isolated splenic CD8+ T cells from young (3–4 months), old (18–20 months), and caloric restricted old (18–20 months) mice in groups of 5 animals. Density of the bands was quantified using a phosphoimager. (A) Histogram showing the composite data of 4 experiments (total 20 animals in each condition). The results represent the mean ± SEM of the relative CD8+ T cell chemokine receptor gene expression level of old and old caloric restricted mice compared to those from the young cohort (arbitrarily defined as equal to 1). (B) CCR7 expression was also determined using a custom CCR7 RPA probe. The left panel is a representative autoradiograph (lane 1 = young CD8+ T cells; lane 2 = old CD8+ T cells; lane 3 = caloric restricted old CD8+ T cells). The right panel represents the composite data of 3 RPAs with a total of 15 animals in each group. Results are presented as mean ± SEM. CR = caloric restricted. Gel loading is corrected with L32 expression.
Mentions: Caloric restriction has been shown to prolong life in mice and to restore many of the aging-associated defects in T cell immune functions [26]. In addition, caloric restriction may affect CD4+ T cell chemokine receptor gene expression in aging [21]. In the current study we did not see any significant effect of caloric restriction on CD8+ T cell chemokine receptor expression compared to ad lib fed mice (Figure 3A). Although the CD8+ T cell CCR1, CCR3 and CXCR4 expression in caloric restricted mice approximates that seen in the young mice, the results did not reach statistical significance. We also examined the effect of caloric restriction on CCR7 expression using a custom RPA probe set as before [21]. The results show reduced CCR7 expression in old CD8+ T cells, similar to that reported in CD4+ T cells in aging [21,27]. Interestingly, caloric restriction selectively prevents the loss of CCR7 expression in CD8+ T cells (Figure 3B).

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