Malignant B Cells Induce the Conversion of CD4+CD25− T Cells to Regulatory T Cells in B-Cell Non-Hodgkin Lymphoma

Recent evidence has demonstrated that regulatory T cells (Treg) were enriched in the tumor sites of patients with B-cell non-Hodgkin lymphoma (NHL). However, the causes of enrichment and suppressive mechanisms need to be further elucidated. Here we demonstrated that CD4(+)CD25(+)FoxP3(+)CD127(lo) Treg were markedly increased and their phenotypes were different in peripheral blood (PB) as well as bone marrow (BM) from newly diagnosed patients with B-cell NHL compared with those from healthy volunteers (HVs). Involved lymphatic tissues also showed higher frequencies of Treg than benign lymph nodes. Moreover, the frequencies of Treg were significantly higher in involved lymphatic tissues than those from PB as well as BM in the same patients. Suppression mediated by CD4(+)CD25(+) Treg co-cultured with allogeneic CFSE-labeled CD4(+)CD25(-) responder cells was also higher in involved lymphatic tissues from B-cell NHL than that mediated by Treg from HVs. In addition, we found that malignant B cells significantly induced FoxP3 expression and regulatory function in CD4(+)CD25(-) T cells in vitro. In contrast, normal B cells could not induce the conversion of CD4(+)CD25(-) T cells to Treg. We also showed that the PD-1/B7-H1 pathway might play an important role in Treg induction. Taken together, our results suggest that malignant B cells induce the conversion of CD4(+)CD25(-) T cells to Treg, which may play a role in the pathogenesis of B-cell NHL and represent a promising therapeutic target.