sq-23377 and Graft-vs-Host-Disease

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).. G-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(+)CD25(high)Foxp3(+) 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.. The percentage of CD4(+)CD25(high)CD127(-/dim)CD62L(+) 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(+)CD25(high)Foxp3(+) 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(+)CD25(high)CD127(-/dim) regulatory T cells were lower in G-BM than that in G-PB (P = 0.014).. In 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.

Topics: Adolescent; Adult; Antigens, CD; Antigens, Differentiation, T-Lymphocyte; Bone Marrow Cells; Bone Marrow Transplantation; CD4-Positive T-Lymphocytes; Female; Flow Cytometry; Graft vs Host Disease; Granulocyte Colony-Stimulating Factor; Humans; Immunophenotyping; Interferon-gamma; Interleukin-17; Interleukin-2 Receptor alpha Subunit; Interleukin-7 Receptor alpha Subunit; Ionomycin; Ki-67 Antigen; Lectins, C-Type; Male; Middle Aged; Peripheral Blood Stem Cell Transplantation; T-Lymphocytes, Regulatory; Tetradecanoylphorbol Acetate; Transplantation, Homologous; Young Adult

Topics: Fetal Blood; Graft vs Host Disease; Humans; Interferon-gamma; Interleukin-2; Ionomycin; Lymphocyte Activation; T-Lymphocytes; Tetradecanoylphorbol Acetate