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

Abstract

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.

Estrogen Regulates CCR Gene Expression and Function in T Lymphocytes

“…Aged (18 -20 mo) female mice were obtained from the National Institute on Aging aged rodent colonies through Harlan Sprague Dawley. As before, only animals without evidence of cancer or lymphoma were used for the experiments (13). Eight-to 10-wk-old oophorectomized C57BL/6 female mice were also obtained from The Jackson Laboratory.…”

“…Splenic CD4 ϩ T cells were isolated from male and female mice as before (13,14). CD4 ϩ T cells were isolated by magnetic cell separation (MACS) MicroBeads technology (Miltenyi Biotec) according to the manufacturer's instructions.…”

“…RNase protection assay (RPA) 3 Quantitative measurements of T cell chemokine receptor gene expression were done by RPA as before using BD Pharmingen kits (13)(14)(15). Pooled RNAs from an equal number of purified T cells from male and female mice in groups of four to six animals were used to minimize individual variability.…”

The Lamina Adventitia Is the Major Site of Immune Cell Accumulation in Standard Chow-Fed Apolipoprotein E–Deficient Mice

“…Experiments spanning the entire life until old age may help to delineate age-related mechanisms of atherogenesis. 21,22 Most studies related to adaptive immunity of atherosclerosis focused on characterization of intima lesions though adventitial inflammation may participate in arterial wall pathology 3,7,23,24 and a role of the adventitia in atherogenesis has also received attention. [25][26][27] However, little information is available on adventitia inflammation and immunity in hyperlipidemic mice as a function of age.…”

Transcriptome analysis of age-, gender- and diet-associated changes in murine thymus

“…Similar studies have now been initiated to examine age-related changes in a number of tissues and cellular subsets by microarray analysis in an effort to identify genes or patterns of gene expression associated with physiological aging, lifespan, and age-related disease states [27,[38][39][40][41][42]. Only a few studies to date have focused on immunologic aging with the majority of studies focusing on an examination of bulk T-cell populations [43]. Limited replication of analysis, small sample sizes and poor array validation have restricted the interpretation of such data with regard to age-related immunological changes.…”