Regulatory T Cells and Extracorporeal Photochemotherapy: Correlation With Clinical Response and Decreased Frequency of Proinflammatory T Cells

BACKGROUND: Immune mechanisms of extracorporeal photochemotherapy (ECP) in refractory/resistant graft-versus-host disease (GvHD) are complex. We have previously analyzed the role of CD4CD25Foxp3 regulatory T cells (T-regs). METHODS: In the current study, we have enlarged the size of the population (n=27; chronic GvHD=18, acute GvHD=9) for a median follow-up of 24 months. T-regs were monitored for CD4, CD25, glucocorticoid-induced tumor necrosis factor receptor (GITR), CD62L, CCR7, Foxp3, and STAT-5. Immune analysis by interleukin (IL)-17 Elispot was carried out on circulating T-helper CD4 cells secreting IL-17, a subset of T cells considered relevant in the pathogenesis of GvHD. RESULTS: We confirm that ECP is accompanied by a significant increase of CD4CD25Foxp3GITRCD62LCCR7 T-regs. Sorted T-regs show augmented phosphorylation of STAT-5. Only ECP-responding patients demonstrate a raise of circulating T-regs, being mostly affected by chronic GvHD. Moreover, this phenomenon corresponds to a diminished secretion of IL-17. DISCUSSION: In conclusion, our study shows that T-regs represent important immune mediators of the clinical benefits of ECP in patients affected by GvHD.