Reproducible alterations of DNA methylation at a specific population of CpG islands during blast formation of peripheral blood lymphocytes.

We investigated the changes in the methylation patterns of CpG islands associated with blast formation of human peripheral blood lymphocytes activated by anti-CD3 and interleukin-2 (IL-2), using restriction landmark genomic scanning with a methylation-sensitive restriction enzyme (RLGS-M) system. Of about 2,100 NotI spot/loci which were analyzed, only 10 showed changes, whereas drastic changes have been observed in cases of malignant and SV40 transformation. These changes were highly reproducible for samples from both the same and different individuals. Even the timing of the changes after cultivation was the same. Thus, we concluded that at least the genomic DNA methylation state in vivo was essentially retained in T blast cells activated in vitro by induction with IL-2 and anti-CD3, which are commonly used in biological experiments as well as clinical diagnosis and therapy.