The Effect of Donor CD4⁺CD25⁺ Regulatory T Cells on Hematopoietic and Immune Reconstitution, GVHD and Disease-Free Survival after Allogeneic Hematopoietic Stem Cell Transplantation.

Objectives To explore the effect of donor CD4⁺CD25⁺ regulatory T cells (T_Reg) on hematopoietic reconstitution, immune reconstitutuion and GVHD in patients who received allogeneic hematopoietic stem cell transplantation (allo-HSCT).

Methods 30 patients were divided into high T_Reg cell group (T_Reg≥10.0×10⁶ cells/kg) and low T_Reg cell group (T_Reg<10.0×10⁶ cells/kg) according to the number of T_Reg cells in the grafts. 13 patients were in high T_Reg cell group and 17 in low T_Reg cell group. The patients details of the two groups are in the following table. Flow cytometry (FCM) was used to continuously detect the percentage of T_Reg cells in the graft, T lymphocyte subsets and T_Reg cells in the recipients’ peripheral blood at different time after allo-HSCT. The hematopoietic reconstitution, immune reconstitution, T_Reg cell reconstitution, the incidence of GVHD and the disease-free survival were observed in the two groups.

Results The reconstitution of WBC and plantelet of high T_Reg cell group and low T_Reg cell group were 8.62±2.293 and 8.88±2.713, 12.69±5.736 and 15.18±16.708 days, respectively, and differed little between the two groups (P value was 0.778, 0.613, respectively). The incidence of acute GVHD (aGVHD) in high T_Reg cell group (15.38%) was obviously lower than that in low T_Reg cell group (58.82%) (P=0.016). There was significantly negative correlation (r=−0.382, P=0.037) between the number of infused donor T_Reg cells and severity of aGVHD. The reconstitution of CD4⁺CD3⁺T, CD45RO⁺CD4⁺T cells at 15 days and CD3⁺T, CD4⁺CD3⁺T cells at 30 days in high T_Reg cell group were notably faster than those in low T_Reg cell group after allo-HSCT (P value was 0.039, 0.024, 0.014, 0.020, respectively). The reconstitution of T_Reg cells at 15 and 180 days were significantly faster than those in low T_Reg cell group after allo-HSCT (P value was 0.013, 0.005, respectively). The 2-year disease-free survival of high T_Reg cell group and low T_Reg cell group were (69.90±15.50)% and (85.60±9.50)%, respectively, and there were no significantly difference between the two groups (P=0.514).

Conclusion T_Reg cells could contribute to decreasing the incidence of aGVHD, promoting immune reconstitution and T_Reg cells reconstitution.