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* Divisions of Geriatric Medicine and Rheumatology, Department of Internal Medicine, and
Department of Pediatrics, University of Michigan, Ann Arbor, MI 48109
Changes in chemokine receptor expression are important in
determining T cell migration and the subsequent immune response. To
better understand the contribution of the chemokine system in immune
senescence we determined the effect of aging on CD4+ T cell
chemokine receptor function using microarray, RNase protection assays,
Western blot, and in vitro chemokine transmigration assays. Freshly
isolated CD4+ cells from aged (20–22 mo) mice were found
to express a higher level of CCR1, 2, 4, 5, 6, and 8 and CXCR2–5, and
a lower level of CCR7 and 9 than those from young (3–4 mo) animals.
Caloric restriction partially or completely restored the aging effects
on CCR1, 7, and 8 and CXCR2, 4, and 5. The aging-associated differences
in chemokine receptor expression cannot be adequately explained by the
age-associated shift in the naive/memory or Th1/Th2 profile.
CD4+ cells from aged animals have increased chemotactic
response to stromal cell-derived factor-1 and macrophage-inflammatory
protein-1
, suggesting that the observed chemokine receptor
changes have important functional consequences. We propose that the
aging-associated changes in T cell chemokine receptor expression may
contribute to the different clinical outcome in T cell chemokine
receptor-dependent diseases in the elderly.
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