Aging Is Associated With Increased T-Cell Chemokine Expression in C57Bl/6 Mice

To better understand the contribution of the chemokine system in immune senescence, we determined the aging effect on CD4+ and CD8+ T-cell chemokine expression by microarray screening and ribonuclease protection assays. Compared with young C57BL/6 mice, freshly isolated CD4+ cells from aged mice express increased level of interferon-gamma-inducible protein 10 (IP-10), macrophage inflammatory protein (MIP)-1alpha, MIP-1beta, regulated upon activation, normal T-cell expressed and secreted (RANTES), and lymphotactin (Ltn). T-cell receptor (TCR)/coreceptor stimulation up-regulates MIP-1alpha, MIP-1beta, and Ltn, and down-regulates IP-10 and RANTES expression in CD4+ T cells. A similar increase in chemokine expression was demonstrated in the CD8+ T cell. Enzyme-linked immunosorbent assays confirmed increased T-cell chemokine protein production in old CD4+ and CD8+ T cells. Finally, supernatant of cultured T cells from old animals caused an enhanced leukocyte chemotaxis response compared with that from young animals, suggesting that the age-related difference in T-cell chemokine expression has an important functional consequence.