Primary Study on the Reconstitution of CD4⁺CD25^high Regulatory T Cells Early after Allogeneic Hematopoietic Stem Cell Transplantation.

Background: CD4⁺CD25⁺ regulatory T cell has been found to play an important role in suppressing allogenetic immune response and controlling GVHD recently. Our study was to explore the reconstitution of CD4⁺CD25^high regulatory T cells early after allogeneic hematopoietic stem cell transplantation(allo-HSCT), and to evaluate its role in the development of acute Graft-versus- host disease(aGVHD)

Methods :27 patients undergoing allo-HSCT were enrolled. Detect the CD4⁺CD25^high T cells subpopulation ratios in CD4⁺ T lymphocytes(CD4⁺CD25^high/CD4⁺)with Flow cytometry, and the expression of FOXP3 mRNA with Real-time PCR assays in the donor grafts and periperal blood frequently after transplantation(at 2 weeks,1 month,2 month,3 month post-transpant,at the onset of aGVHD,and when aGVHD was controlled.).

Results:

1. In without aGVHD group, the CD4⁺CD25^high/CD4⁺ ratio increased significantly at 2 weeks post-transplant, and decreased later(P<0.05); the expression of FOXP3 increased significantly early after transplantation, but remained below the healthy-control level within 3 months after transplantation(P<0.05).

2. In aGVHD-group, the CD4⁺CD25^high/CD4⁺ ratio also increased significantly at 2 weeks post-transplant,but exhibited no decrease tendency later(P<0.05);moreover the expression of FOXP3 remained low(P<0.05),and was lower than the without-aGVHD-group at 1∼3month post-transplant(P<0.05).

3. At the onset of aGVHD, the CD4⁺CD25⁺ /CD4⁺ and the CD4⁺CD25^high/CD4⁺ ratios were both higher than the healthy control and without-aGVHD group(P<0.05),but the expression of FOXP3 were lower than that of healthy control and without-aGVHD group(P<0.05);when aGVHD was controlled, the expression of FOXP3 raised compared with that at the onset of aGVHD(P=0.025), also the CD4⁺CD25^high/CD4⁺ ratio exhibited an increase tendency(P=0.050).

Conlusion:

1. The CD4⁺CD25^high regulatory T cells subpopulation undergo a significant expansion early after transplantation, but its complete reconstitution is a long-term process.

2. The lower number of CD4⁺CD25^high regulatory T cells and/or their lower expression of FOXP3 gene may be related with the development of aGVHD.