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

Raymond Yung¹^,2 , RuRan Mo¹ , Annabelle Grolleau-Julius¹ and Mark Hoeltzel³

¹Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA

²Geriatrics Research, Education and Clinical Center, Ann Arbor Veteran Affairs Medical Center, Ann Arbor, MI, USA

³Department of Pediatrics, University of Michigan, Ann Arbor, MI, USA

author email corresponding author email

Immunity & Ageing 2007, 4:8doi:10.1186/1742-4933-4-8


Published:	14 November 2007

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 α(MIP-1α). 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.