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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

Murine CD8+ T cell chemokine receptor gene expression following T cell receptor/CD28 stimulation. Autoradiographs of representative ribonuclease protection assay (RPA) showing the effect of aging and anti-CD3/anti-CD28 monoclonal antibody (mAb) stimulation on murine CD8+ T cell CCR1–5 (A) and CXCR2, 4 and 5 (B) gene expression. Lane 1 in Figure 2A and Lane 2 in Figure 2B = Young (3–4 months) unstimulated cells; Lane 2 in Figure 2A and Lane 3 in Figure 2B = Old (18–20 months) unstimulated cells; Lane 3 in Figure 2A and Lane 4 in Figure 2B = Young cells after 72 hours of anti-CD3/anti-CD28 mAb stimulation; Lane 4 in Figure 2A and Lane 5 in Figure 2B = Old cells after 72 hours of anti-CD3/anti-CD28 mAb stimulation; Lane 5 in Figure 2A and Lane 1 in Figure 2B = unprotected probe set. Composite histogram (C) of 3 RPAs using pooled RNA from a total of 15 animals in each age group is shown. Gel loading is corrected with L32 expression.
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Figure 2: Murine CD8+ T cell chemokine receptor gene expression following T cell receptor/CD28 stimulation. Autoradiographs of representative ribonuclease protection assay (RPA) showing the effect of aging and anti-CD3/anti-CD28 monoclonal antibody (mAb) stimulation on murine CD8+ T cell CCR1–5 (A) and CXCR2, 4 and 5 (B) gene expression. Lane 1 in Figure 2A and Lane 2 in Figure 2B = Young (3–4 months) unstimulated cells; Lane 2 in Figure 2A and Lane 3 in Figure 2B = Old (18–20 months) unstimulated cells; Lane 3 in Figure 2A and Lane 4 in Figure 2B = Young cells after 72 hours of anti-CD3/anti-CD28 mAb stimulation; Lane 4 in Figure 2A and Lane 5 in Figure 2B = Old cells after 72 hours of anti-CD3/anti-CD28 mAb stimulation; Lane 5 in Figure 2A and Lane 1 in Figure 2B = unprotected probe set. Composite histogram (C) of 3 RPAs using pooled RNA from a total of 15 animals in each age group is shown. Gel loading is corrected with L32 expression.

Mentions: Chemokine receptor expression profile is altered following the engagement of the TCR to the major histocompatibility complex (MHC) on antigen presenting cells. For example, receptors for constitutively expressed chemokines such as CXCR4 and CCR7 are down-regulated as naïve T cells are activated and differentiated into effector cells [22]. This in turn allows the CD8+ T cells to migrate to peripheral tissues to perform their effector function. Others have reported that specific T cell dysfunctions in aging can also be rescued by co-activating the TCR and T cell co-stimulation pathways [23-25]. We therefore determined the combined effect of T cell receptor (CD3)/costimulatory molecule (CD28) stimulation on young and old CD8+ T cell chemokine receptor expression profile (Figure 2). The results show that the CD8+ T cells CCR1, 2, 3, 5 and CXCR2, 4, 5 gene expression decreases after the CD3/CD28 activation. CCR4 is the only chemokine receptor that showed increased expression following anti-CD3/anti-CD28 mAb treatments, similar to what has been seen in CD4+ T cells [21]. Despite the age difference in basal chemokine receptor gene expression level, old CD8+ T cells exhibit similar robust CC and CXC chemokine receptor response to TCR/co-stimulatory activation as young 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)

Murine CD8+ T cell chemokine receptor gene expression following T cell receptor/CD28 stimulation. Autoradiographs of representative ribonuclease protection assay (RPA) showing the effect of aging and anti-CD3/anti-CD28 monoclonal antibody (mAb) stimulation on murine CD8+ T cell CCR1–5 (A) and CXCR2, 4 and 5 (B) gene expression. Lane 1 in Figure 2A and Lane 2 in Figure 2B = Young (3–4 months) unstimulated cells; Lane 2 in Figure 2A and Lane 3 in Figure 2B = Old (18–20 months) unstimulated cells; Lane 3 in Figure 2A and Lane 4 in Figure 2B = Young cells after 72 hours of anti-CD3/anti-CD28 mAb stimulation; Lane 4 in Figure 2A and Lane 5 in Figure 2B = Old cells after 72 hours of anti-CD3/anti-CD28 mAb stimulation; Lane 5 in Figure 2A and Lane 1 in Figure 2B = unprotected probe set. Composite histogram (C) of 3 RPAs using pooled RNA from a total of 15 animals in each age group is shown. 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 2: Murine CD8+ T cell chemokine receptor gene expression following T cell receptor/CD28 stimulation. Autoradiographs of representative ribonuclease protection assay (RPA) showing the effect of aging and anti-CD3/anti-CD28 monoclonal antibody (mAb) stimulation on murine CD8+ T cell CCR1–5 (A) and CXCR2, 4 and 5 (B) gene expression. Lane 1 in Figure 2A and Lane 2 in Figure 2B = Young (3–4 months) unstimulated cells; Lane 2 in Figure 2A and Lane 3 in Figure 2B = Old (18–20 months) unstimulated cells; Lane 3 in Figure 2A and Lane 4 in Figure 2B = Young cells after 72 hours of anti-CD3/anti-CD28 mAb stimulation; Lane 4 in Figure 2A and Lane 5 in Figure 2B = Old cells after 72 hours of anti-CD3/anti-CD28 mAb stimulation; Lane 5 in Figure 2A and Lane 1 in Figure 2B = unprotected probe set. Composite histogram (C) of 3 RPAs using pooled RNA from a total of 15 animals in each age group is shown. Gel loading is corrected with L32 expression.
Mentions: Chemokine receptor expression profile is altered following the engagement of the TCR to the major histocompatibility complex (MHC) on antigen presenting cells. For example, receptors for constitutively expressed chemokines such as CXCR4 and CCR7 are down-regulated as naïve T cells are activated and differentiated into effector cells [22]. This in turn allows the CD8+ T cells to migrate to peripheral tissues to perform their effector function. Others have reported that specific T cell dysfunctions in aging can also be rescued by co-activating the TCR and T cell co-stimulation pathways [23-25]. We therefore determined the combined effect of T cell receptor (CD3)/costimulatory molecule (CD28) stimulation on young and old CD8+ T cell chemokine receptor expression profile (Figure 2). The results show that the CD8+ T cells CCR1, 2, 3, 5 and CXCR2, 4, 5 gene expression decreases after the CD3/CD28 activation. CCR4 is the only chemokine receptor that showed increased expression following anti-CD3/anti-CD28 mAb treatments, similar to what has been seen in CD4+ T cells [21]. Despite the age difference in basal chemokine receptor gene expression level, old CD8+ T cells exhibit similar robust CC and CXC chemokine receptor response to TCR/co-stimulatory activation as young 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