[The role of CD4+ CD25+ T cell and FOXP3 in hsot acute graft rejection]

Abstract

Objective: To explore the relationship among CD4+ CD25+ regulatory T cell, the expression of FOXP(3) mRNA levels of donor bone marrow (BM) and graft versus host disease (GVHD) in allogeneic hematopoietic stem cell transplantation (allo-HSCT).

Methods: (1) Thirty patients undergoing allo-HSCT were enrolled in this study. The levels of donor CD4+CD25+ regulatory T cell were compared in the patients with GVHD and those without GVHD with immunofluorescence and flow cytometry. (2) The donor BM expressions of FOXP(3) mRNA levels were analyzed by using reverse transcriptase polymerase chain reaction (RT-PCR).

Results: (1) All patients achieved engraftment. The median time for ANC > or = 0.5 x 10(9)/L and PLT > or = 20 x 10(9)/L were attained at day 14 (range, 12-15) and day 18 (range, 15-25) respectively. With a median follow-up of 12.8 (8-16) months, acute GVHD (aGVHD) occurred in 15 of the 30 patients (50.0%) with grade II-IV aGVHD (40.0%). Chronic GVHD developed in 6 (extensive 2, limited 4) out of the 30 patients (20.0%). (2) The levels of donor CD4+CD25+ regulatory T cell pre-and post-mobilization were (2.67 +/- 0.38)% and (5.01 +/- 1.33)% respectively; no difference was observed (P > 0.05). (3) Patients with I-II aGVHD demonstrated higher donor-type CD4+CD25+ immune regulatory T cell level than those with III-IV aGVHD. Patients with III-IV aGVHD showed much lower donor-type CD4+CD25+ immune regulatory T cell level than those without GVHD. No difference was observed between the patients withI-II aGVHD and those without aGVHD. (4) The transcripts of FOXP(3) donor BM were detected in seven donors for the thirty recipients who received allo-HSCT. Among the seven patients who received stem cells from these donors five had no GVHD after transplantation and the remaining two developed I aGVHD. Donor BM FOXP(3) transcripts were never detected in patients with II-IV aGVHD.

Conclusions: (1) Donor-type CD4+CD25+ immune regulatory T cell level was related to recipient II-IV aGVHD. Up-grade donor-type CD4+CD25+ immune regulatory T cell level could reduce the incidence of aGVHD. (2) Donor BM FOXP(3) transcripts were detected in patients without serious aGVHD after transplantation.