Abstract
BackgroundRegulatory T cells (Treg) in allografts are important for the prevention of graft-versus-host disease (GVHD) post-transplantation. The aim of this study was to compare the contents of Tregs and effector T cells in granulocyte colony-stimulating factor (G-CSF)-primed bone marrow grafts (G-BM) and peripheral blood grafts (G-PB).MethodG-BM and G-PB were obtained from 20 allogeneic donors. T-cell subgroups, including conventional T cells and different types of Treg cells, as well as the percentage of Ki67 expression on CD4+CD25highFoxp3+ Treg cells, were analyzed using flow cytometry. The levels of interferon-γ (IFN-γ) and interleukin-17 (IL-17) secreted by T cells stimulated with PMA and ionomycin were also determined by flow cytometry.ResultsThe percentage of CD4+CD25highCD127-/dimCD62L+ Treg cells was significantly higher in the G-BM group, with higher proportions of CD45RA+ naïve Treg cells and higher expression of CD69 on Treg cells in G-BM (P < 0.05). The percentage of Ki67 expression in CD4+CD25highFoxp3+ Treg cells in G-BM was significantly higher than that on G-PB. The suppressive functions of Treg cells in inhibiting T-cell activation were comparable between G-BM and G-PB. The proportions of CD4+CD25−CD69+ Treg subsets as well as Th1 cells in G-BM were also significantly higher than those in G-PB (P < 0.001). The proportions of conventional T cells and Th17 effector cells were comparable in G-BM compared with those in G-PB. Thus, the ratio of conventional T cells and CD4+CD25highCD127-/dim regulatory T cells were lower in G-BM than that in G-PB (P = 0.014).ConclusionIn addition to the much higher T-cell counts in G-PB grafts that may contribute to more severe GVHD, the higher frequency of Treg cells and lower ratio of conventional T cells to Treg cells in G-BM compared with G-PB grafts might reduce GVHD post-transplantation in G-BM compared with G-PB transplantation.Electronic supplementary materialThe online version of this article (doi:10.1186/s12967-015-0507-z) contains supplementary material, which is available to authorized users.
Highlights
Allogeneic hematopoietic stem cell transplantation is the only curative method available for malignant hematologic diseases
Because of the significantly higher numbers of CD4+ T cells in G-PB compared to G-bone marrow (BM), the absolute numbers of CD4+ CD25highCD127-/low regulatory T cells, CD4+CD25high CD62L+ regulatory T cells and CD4+CD25−CD69+ regulatory T cells were significantly lower in G-CSF-primed bone marrow (G-BM) than in G-PB (P < 0.0001, Figure 1E)
Comparison of the ratio of regulatory T cells and effector T cells between G-BM and G-PB We found no statistically significant differences comparing G-BM and G-PB with respect to the proportions of CD4+ T cells with a conventional T cell phenotype (CD4+ CD25lowCD127+; 75.60% ± 5.41% vs. 73.99% ± 7.97%, P = 0.247, Figure 5A) and Th17 cells (3.86% ± 1.96% vs. 2.79% ± 1.40%, p = 0.126, Figure 5B)
Summary
Allogeneic hematopoietic stem cell transplantation (alloHSCT) is the only curative method available for malignant hematologic diseases. Its broad application is limited by the high incidence of graft-versus-host disease (GVHD). Rezvanietal et al determined that increased frequencies of CD4+Foxp3+ Treg cells in the peripheral blood of the donor negatively correlated with the incidence of GVHD in the graft recipient [4]. Subsequent studies have confirmed this correlation in the recipients of HLA-identical sibling and unrelated donor stem cell grafts [5,6], indicating that infused donor Treg cells in graft contents appear to lessen the severity of GVHD. Donor immunoregulatory T cells, including CD4+CD25highCD62L+ regulatory T cells and CD4+ CD25−CD69+ T cells, contribute to decreased acute GVHD post-transplantation [7,8,9]. Regulatory T cells (Treg) in allografts are important for the prevention of graft-versus-host disease (GVHD) post-transplantation. The aim of this study was to compare the contents of Tregs and effector T cells in granulocyte colony-stimulating factor (G-CSF)-primed bone marrow grafts (G-BM) and peripheral blood grafts (G-PB)
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