T cell chemokine receptor expression in aging.
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-1alpha, 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.
Mo
Ruran
R
Division of Geriatric Medicine, Department of Internal Medicine, University of Michigan, Ann Arbor 48109, USA.
Chen
Jun
J
Han
Yin
Y
Bueno-Cannizares
Cecelia
C
Misek
David E
DE
Lescure
Pascal A
PA
Hanash
Samir
S
Yung
Raymond L
RL
D000375:Aging / Q000235:genetics / Q000276:immunology*; D000818:Animals; D015153:Blotting, Western; D031204:Caloric Restriction; D002478:Cells, Cultured; D002634:Chemotaxis, Leukocyte; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D015347:RNA Probes; D020871:RNA Stability / Q000276:immunology; D012333:RNA, Messenger / Q000378:metabolism; D019707:Receptors, Chemokine / Q000096:biosynthesis* / Q000235:genetics; D012260:Ribonucleases; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology* / Q000378:metabolism* / Q000502:physiology; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism
D015347:RNA Probes; D012333:RNA, Messenger; D019707:Receptors, Chemokine; D012260:Ribonucleases