Age-associated alterations in inducible gene transcription in human CD4(+) T lymphocytes

Age associated immune dysregulation results in a pro-inflammatory state and increased susceptibility to infections and autoimmune diseases. Studies show that signaling initiated at the T cell antigen receptor (TCR) is impaired in CD4(+) T cells from old compared to young mice. Here we examined TCR-inducible gene expression changes in CD4(+) T cells during human aging. We reveal a dichotomy in gene expression mediated by the inducible transcription factor NF-κB. Most NF-κB target genes are not induced in a sustained manner in cells derived from older compared to younger individuals. However, a subset of NF-κB target genes including genes associated with chronic pro-inflammatory state in the elderly, such as interleukin 1 and 6, continue to be up-regulated even in the absence of NF-κB induction. In addition, we identify other widespread changes in gene expression between cells derived from older and younger individuals. Surprisingly, many of the most noteworthy age-associated changes in human CD4(+) T cells differ from those seen in murine models. Our studies provide the first view of age-associated alteration of TCR-inducible gene expression in human CD4(+) T cells.