The DNA mismatch repair system, the main postreplicative correction pathway in eukaryotic cells, has been shown to be involved in the acquisition of genetic damage during the aging of normal somatic cells, including those of the immune system. Previously, we showed that some but not all human T cell clones (TCC) in an in vitro culture aging model develop microsatellite instability (MSI), which is associated with altered expression of mismatch repair genes. Here, we analyzed levels of mismatch repair proteins as well as the corresponding mRNAs and related this to the development of microsatellite instability in TCC. Msh2, Msh3, Msh6, Pms1, and Pms2 protein expression was quantified by Western blotting. We found that clones not manifesting microsatellite instability in this in vitro model of T cell replicative aging, induced by persistent antigenic stimulation, maintain normal transcriptional control and coordination among the mismatch repair system genes, while clones which do manifest MSI display a general deregulation of gene expression, which is likely to contribute to its occurrence.
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