Reciprocal Modulation of Circulating CD4+CD25+^bright T Cells Induced by Extracorporeal Photochemotherapy in Cutaneous T-Cell Lymphoma and Chronic GRAFT- Versus-Host-Disease Patients

The mechanisms of action of extracorporeal photochemotherapy (ECP) in cutaneous T-cell lymphoma (CTCL) are poorly understood. Recently, ECP has been shown to induce an increase in regulatory T cell (Treg) expression and functional activities in Graft-versus-host-disease (GvHD), whereas no data are available in CTCL patients. The aim of this study is to evaluate whether ECP is able to modulate the expression levels of the circulating CD4+CD25+bright subset in CTCL patients and whether these modifications are related to the disease course. The patient population included 43 CTCL and 15 chronic GvHD patients treated by ECP at our institutions since 1992. The expression of the circulating CD4+CD25+bright subset was analysed at baseline and sequentially during treatment by flow-cytometry. Fifty healthy donors were used as controls. The baseline circulating CD4+CD25+bright percentage values in CTCL (median: 4.3%) were similar to those of healthy donors, whereas GvHD showed significantly lower values (median: 1.5%; p<0.001). During treatment, CTCL patients were characterised by an early decrease (from 4.3% to 2.4% median after 6 months). The CD4+CD25+bright decrease was associated to the disease course, as it occurred in 91.3% of responding but in only 25% of PD patients (p=0.0001). On the other hand, a significant increase of CD4+CD25+bright cells was observed in GvHD. ECP induces a reciprocal modulation of the circulating CD4+CD25+bright cells in CTCL and GvHD, with a downregulation in CTCL potentially associated with the response mechanisms.