TCRbeta Gene Rearrangements for Detection and Monitoring of Minimal Residual Disease after Allogenic Stem-Cell Transplantation in Patients with Advanced Mycosis Fungoides and Sézary Syndrome

The effector T-cell lineage shows great plasticity. Th17 cells are acknowledged to be instrumental in the response against microbial infection, but are also associated with autoimmune inflammatory processes. Here, we report that human regulatory T cells (CD4P posCD25 highFoxp3 posCD127 negCD27P pos) can differentiate into IL-17-producing cells, when stimulated by allogeneic antigenpresenting cells, especially monocytes. in the presence of rhl L-2/rhl L-15. These regulatory T cell (Treg)-derived IL-17-producing cells showed high expression of the Th17-related transcription factor RORγt and were positively identified by CCR6 expression. This differentiation process was enhanced by exogenous IL-1β, IL-23, and IL-21, whereas IL-6 or TGFβ did not affect the emergence of IL-17-producing cells. The addition of IL-1 receptor antagonist (IL-1Ra), but not anti-IL-23 antibody, reduced IL-17-producing cell numbers. When an histone deacetylase (HDAC) inhibitor trichostatin A (TSA) was evaluated, we found a profound negative effect on the emergence of IL-17-producing cells from Tregs, implying that Treg differentiation into IL-17-producing cells depends on histone/protein deacetylase activity. Thus, the data suggest that epigenetic modification underlies the phenomenon of Treg plasticity here described