Reduction of Foxp3+ T cell subsets involved in incidence of chronic graft-versus-host disease after allogeneic hematopoietic stem cell transplantation.

Foxp3+ T cells (CD4+ Tregs and CD8+ Treg) have been demonstrated to play roles in the maintenance of tolerance after allogeneic hematopoietic stem cell transplantation (Allo-HSCT). We have found that Foxp3+ γδTCR+ Treg cells (γδTregs) exerted regulatory functions. In the current study, patients were recruited and divided as non-cGVHD, limited cGVHD and extensive cGVHD groups. Healthy volunteers were recruited as healthy group. Treg cells were evaluated by flow cytometry. Serum cytokine levels of IL-2, tumour necrosis factor-α, interferon-γ and transforming growth factor-β1 (TGF-β1) were evaluated by ELISA. The results showed that percentages of CD4+ Tregs, CD8+ Tregs and γδTregs were all significantly increased in non-cGVHD group compared with those in healthy group, limited cGVHD group and extensive cGVHD group. Moreover, compared with extensive cGVHD group, percentages of these three types of Tregs were significantly increased in limited cGVHD group. The levels of TGF-β1 increased dramatically in non-cGVHD group compared with other groups. Spearman's correlation analysis revealed that the increased levels of TGF-β1 and IL-2 were positively associated with increased Treg subsets, indicating that TGF-β1 and IL-2 participated in the expansion process of Foxp3+ Tregs in vivo. Our findings support that increasing the number of Tregs following allo-HSCT would be a preferential strategy for controlling cGVHD.