Rezvani Katayoun, Mielke Stephan, Ahmadzadeh Mojgan, Kilical Yasemin, Savani Bipin N, Zeilah Josette, Keyvanfar Keyvan, Montero Aldemar, Hensel Nancy, Kurlander Roger, Barrett A John
Stem Cell Allogeneic Transplant Section, Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892-1202, USA.
Blood. 2006 Aug 15;108(4):1291-7. doi: 10.1182/blood-2006-02-003996. Epub 2006 Apr 20.
Regulatory T cells (T(reg)s) that constitutively express FOXP3 are instrumental to the maintenance of tolerance and may suppress graft-versus-host disease (GVHD) in humans. To determine whether regulatory T cells in allogeneic stem cell transplants (SCTs) ameliorate GVHD after transplantation, we quantitated the coexpression of FOXP3 on CD4(+) T cells in 32 donor SCTs infused into HLA-matched siblings and examined GVHD incidence in respective recipients. High CD4(+)FOXP3(+) T-cell count in the donor was associated with a reduced risk of GVHD. We monitored T(reg)s during immune reconstitution in 21 patients with leukemia undergoing a T-cell-depleted allogeneic SCT. Early after SCT, there was a significant expansion in the CD4(+)FOXP3(+) T-cell compartment. A low CD4(+)FOXP3(+) T-cell count early after SCT (day 30) was associated with an increased risk of GVHD, and the ratio of CD4(+)FOXP3(+) T cells to CD4(+)CD25(+)FOXP3(-) T cells was significantly reduced in patients with GVHD, suggesting diminished control of effector T cells. Our findings suggest that graft T(reg) content may predict for risk of GVHD after SCT. Determining the T(reg) levels in the donor and manipulating T(reg)s early after transplantation may provide a new approach to controlling GVHD.
组成性表达FOXP3的调节性T细胞（Tregs）有助于维持免疫耐受，并可能抑制人类移植物抗宿主病（GVHD）。为了确定异基因干细胞移植（SCT）中的调节性T细胞是否能改善移植后的GVHD，我们对输注到HLA匹配同胞体内的32例供体SCT中CD4(+) T细胞上FOXP3的共表达进行了定量，并检查了相应受者的GVHD发生率。供体中高CD4(+)FOXP3(+) T细胞计数与GVHD风险降低相关。我们监测了21例接受T细胞去除的异基因SCT的白血病患者免疫重建过程中的Tregs。SCT后早期，CD4(+)FOXP3(+) T细胞区室有显著扩增。SCT后早期（第30天）低CD4(+)FOXP3(+) T细胞计数与GVHD风险增加相关，且GVHD患者中CD4(+)FOXP3(+) T细胞与CD4(+)CD25(+)FOXP3(-) T细胞的比例显著降低，提示效应T细胞的控制减弱。我们的研究结果表明，移植物Treg含量可能预测SCT后GVHD的风险。确定供体中的Treg水平并在移植后早期操纵Tregs可能为控制GVHD提供一种新方法。
