We isolated highly purified CD8+CD28+ and CD8+CD28- T cell populations from healthy young and elderly persons for gene expression profiling using Affymetrix oligonucleotide microarrays. We demonstrate that the gene expression profile of CD8+CD28- T cells is very similar in young and elderly persons. In contrast, CD8+CD28+ in elderly differ from CD8+CD28+ in young persons. Hierarchical clustering revealed that CD8+CD28+ in elderly are located between CD8+CD28+ in young and CD8+CD28- (young and old) T cells regarding their differentiation state. Our study demonstrates a dichotomy of gene expression levels between CD8+CD28+ T cells in young and elderly persons but a similarity between CD8+CD28- T cells in young and elderly persons. As CD8+CD28+ T cells from elderly and young persons are distinct due to a different composition of the population, these results suggest that the gene expression profile does not depend on chronological age but depends on the differentiation state of the individual cell types.