Age-related changes in T cell surface markers: a longitudinal analysis in genetically heterogeneous mice

In a longitudinal design in which each animal was examined repeatedly throughout its life, we used flow cytometry to determine the numbers or proportions of a variety of T lymphocyte subsets in the peripheral blood of mice aged 8-20 months. Half of the 128 mice were given a low calorie diet which is known to extend lifespan and to reduce the rate of age-associated change in T cell immune function. In these genetically heterogeneous mice, bred as the progeny of CB6F1 females and C3D2F1 males, aging led to statistically significant increases in the number of CD3 cells and the proportions of CD4 memory and CD8 memory cells, and declines in the proportions of CD4 cells and CD4 virgin cells. Older mice also had increased proportions of CD4 and CD8 cells that were able to extrude the fluorochrome R123 through the action of P-glycoprotein. Caloric restriction delayed or prevented most of these age-dependent changes, but had little effect on expression of P-glycoprotein. Correlation analysis showed that those individual mice with high levels of CD4 memory or CD8 memory T cells tended also to have relatively low levels of CD4 virgin cells and low proportions of CD4 T cells, particularly at older ages. In addition, those mice which had the greatest rate of increase in CD4 memory and CD8 memory T cells also tended to show the greatest decline in CD4 virgin and in the proportion of CD4 cells. High numbers of CD4R (and high rates of change in the CD4R subset) were associated with high numbers (and change scores) for the CD8R subset, but there were no strong correlations between the R123-extruding subsets and other age-sensitive markers. Thus some, but not all, age-sensitive T cell subsets show correlated levels and correlated rates of change throughout the middle of the lifespan.