The Role Of CD4～+CD25～+ Regulatory T Cell In Allogeneic Hematopoietic Stem Cell Transplantation

Objective: (1) To explore the relationship among CD4~+CD25~+ regulatory T cell, the level of IL-10 and TGF-β and the expression of FOXP3 mRNA levels of donor BM with GVHD in allogeneic hematopoietic stem cell transplantation(allo-HSCT).Methods: (1)From April 2004 to December 2004, forty-two patients undergoing allo-HSCT were enrolled in this study. Peripheral blood(PB) expression of donor before G-CSF mobilization , bone marrow(BM) expression of donor after G-CSF mobilization were analyzed by immnofluorescence and flowcytometry. The levels of donor CD4~+CD25~+ regulatory T cell were compared in the patients with GVHD and those without GVHD. The levels of recipient CD4~+CD25~+ regulatory T cell were detected in the patients with GVHD. (2)The levels of IL-10 and TGF-β were measured in the serum of patients who received allo-HSCT at different stages and 8 normal controls using enzyme linked- immunosorbent assay(ELISA). To explore the relationship between donor CD4~+CD25~+ regulatory T cell and the level of IL-10 and TGF-β in patients with GVHD. (3) To explore the relationship between the expression of FOXP3 mRNA levels of donor BM and GVHD, we first analyzed the expression ofF0XP3 mRNA levels of donor BM using reverse transcriptase polymerase chain reaction(RT-PCR).Results: (l)The levels of CD4+CD25+ regulatory T cell have no difference between donors before and after mobilization; Patients with I °~II° aGVHD demonstrated higher donor-type CD4+CD25+ immune regulatory T cell level than those with III°~IVO aGVHD; Patients with III°~IVO aGVHD demonstrated much lower donor-type CD4+CD25+ immune regulatory T cell level than those without GVHD; The levels of donor-type CD4+CD25+ regulatory T cell have no difference between patients with I °~II° aGVHD and those without aGVHD. (2) The concentrations of IL-10 and TGF-p serum of patients with III°~IVO aGVHD were much lower than those without it; There were no difference between patients with I °~ II ° GVHD and those with III°~IVoaGVHD; The concentrations of TGF-p have no difference between patients with I °~ II ° GVHD and those without GVHD; But the concentrations of IL-10 serum of patients with I °~ II ° aGVHD were much lower than those without it. (3)The transcripts of FOXP3 donor BM were detected in seven donor of thirty recipients who received allo-HSCT. Three developed relapse after transplantation, two developed I °aGVHD after transplantation, and other two recipients without GVHD. donor BM FOXP3 transcripts were never detected in patients with II °~IVO aGVHD. Conclusion: (l)Donor-type CD4+CD25+immune regulatory T cell level wasrelative to recipient aGVHD and cGVHD . Up-grade donor-type CD4+CD25+ immune regulatory T cell level could reduce the incidence of aGVHD and cGVHD. The levels of CD4+CD25+ regulatory T cell of recipient have no difference among three groups of aGVHD. Patients with cGVHD demonstrated higher recipient-type CD4+CD25+ immune regulatory T cell level than those without cGVHD. (2) IL-10 and TGF-p play an important negative role in the development of aGVHD. They could suppress graft versus host reaction. (3) Donor BM FOXP3 transcripts were detected in patients without serious aGVHD after transplantation.