期刊
CLINICAL AND EXPERIMENTAL IMMUNOLOGY
卷 193, 期 3, 页码 386-399出版社
WILEY
DOI: 10.1111/cei.13145
关键词
human DN T-regs; humanized mouse model; xenogeneic GVHD
类别
资金
- Canadian Institutes of Health Research [142199]
Despite the demonstration of potent immunosuppressive function of T cell receptor (TCR)-(+) double-negative regulatory T cells (DN T-regs), scarce numbers and lack of effective expansion method limit their clinical applications. Here we describe an approach that allows for approximate to 3500-fold ex-vivo expansion of human DN T-regs within 3 weeks with >97% purity. Ex-vivo-expanded DN T-regs suppress proliferation of polyclonally stimulated autologous T and B cells in vitro through direct cell-to-cell contact. In vivo, we demonstrate for the first time that infusion of human DN T-regs delayed an onset of xenogeneic graft-versus-host disease (GVHD) significantly in a humanized mouse model. Furthermore, preincubation of ex-vivo-expanded DN T-regs with a mechanistic target of rapamycin (mTOR) inhibitor rapamycin enhanced their immune regulatory function further. Taken together, this study demonstrates that human DN T-regs can be expanded ex vivo to therapeutic numbers. The expanded DN T-regs can suppress proliferation of T and B cells and attenuate GVHD, highlighting the potential clinical use of DN T-regs to mitigate GVHD.
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