A Study On The Relationship Between CD4～+CD25～+T Cells And Acute GVHD After Allo-HSCT

[Objective] Acute graft-versus-host disease (aGVHD) is still a majorobstacle in clinical allogeneic haematopoietic stem cell transplantation (allo-HSCT). Recently a population of CD4~+CD25~+T cells (Treg cells) has been characterized, which controls immunologic reactivity in vivo and which on transfer can prevent experimental acute GVHD in mice model. And these Treg cells can preserve graft-versus-tumor activity while inhibiting graft-versus-host disease. There are 5-10% to express CD25 molecule in ordinary person and small rats peripherial blood and spleen. Here we study the relationship between CD4~+CD25~+ T cell and recipient acute GVHD, furthermore investigate the content of CD62L, CD28, CTLA-4, Foxp3 molecules expressing on these cells.[Methods] 18 patients undergoing allo-HSCT were included in thisstudy. We investigated the number of peripheral blood CD4~+CD25~+ T cells and CD62L,CD28,CTLA-4 molecules expressing on these cells in patients on +21, 31, 41, 51, 61 day after allo-HSCT by three-color flow cytometry. The content of Foxp3 mRNA were measured in CD4~+CD25~+ T cells in the same patients peripheral blood with RT-PCR. The difference between the patients with aGVHD and without aGVHD were analysised.[Results] Patients with aGVHD had markedly elevated numbers ofCD4~+CD25~+T cells as compared to patients without aGVHD (P<0.05) .And the numbers of these cells will increased associated with the development of aGVHD. In contrast to controls, CD4~+CD25~+ T cells derived from patientswith aGVHD were characterized by lower surface CD62L expression ( P<0.05 ) . Foxp3 mRNA expression was significantly decreased in peripheral blood mononuclear cells from patients with aGVHD (P<0.05) . Expression of Foxp3 negatively correlated with the severity of aGVHD. The results suggest that defective thymic function contributes to the impaired reconstitution of immune regulatory mechanisms following transplantation. The decrease in regulatory mechanisms after transplantation appears to provide an environment permissive to the development of aGVHD.