血液树突状细胞趋化因子受体 CCR5 表达的改变与急性移植物抗宿主病相关。

Alterations in chemokine receptor CCR5 expression on blood dendritic cells correlate with acute graft-versus-host disease.

机构信息

1 Flow Cytometry Unit, Institute of Clinical Pathology and Medical Research, Westmead Hospital, Westmead, New South Wales, Australia. 2 Dendritic Cell Biology and Therapeutics Group, ANZAC Medical Research Institute, Concord, New South Wales, Australia. 3 Blood and Marrow Transplant Service, Westmead Hospital, Westmead, New South Wales, Australia. 4 Address correspondence to: Kenneth F. Bradstock, M.B., B.S., P.hD., Haematology Department Westmead Hospital, Darcy Rd, Westmead, New South Wales, Australia 2145.

出版信息

Transplantation. 2013 Oct 27;96(8):753-62. doi: 10.1097/TP.0b013e31829e6d5b.

DOI:10.1097/TP.0b013e31829e6d5b

PMID:23903010

Abstract

BACKGROUND

Dendritic cells (DC) are important in the development of acute graft-versus-host disease (GVHD) after allogeneic hemopoietic cell transplantation (alloHCT). The trafficking of immature DC from blood to GVHD target organs is likely to be regulated by chemokine receptors.

METHODS

We performed flow cytometry to document the expression of chemokine receptors on circulating DC and correlated the findings after alloHCT with occurrence of acute GVHD.

RESULTS

In normal individuals, plasmacytoid DC (pDC) expressed high levels of CCR5, whereas the major CD16 myeloid DC subpopulation lacked CCR5. However, its expression on CD16 cells was induced by culture in allogeneic mixed lymphocyte reaction supernatant, an effect largely mediated by interferon-γ. CCR5 was expressed on a significant proportion of CD16 DC in 42 alloHCT patients, whereas it was down-regulated on pDC. The maximum percentage of CCR5CD16 DC, at any time after transplantation, correlated with acute GVHD, whereas the minimum CCR5 on pDC showed a similar correlation. Before developing signs of GVHD, the maximum percentage CCR5CD16 DC was higher in patients with GVHD grades II to IV than in GVHD grades 0 and I, whereas the minimum percentage CCR5 on pDC was lower in GVHD grades II to IV than in GVHD grades 0 and I. CCR5 levels more than 20.5% on CD16 myeloid DC and less than 22.6% on CD123 pDC correlated with subsequent GVHD grades II to IV with high sensitivities and specificities.

CONCLUSIONS

These observations may reflect DC activation and altered homing during the alloimmune response and could allow early diagnosis and therapeutic intervention before the clinical diagnosis of GVHD.

摘要

背景

树突状细胞（DC）在异基因造血细胞移植（alloHCT）后急性移植物抗宿主病（GVHD）的发展中很重要。未成熟 DC 从血液向 GVHD 靶器官的迁移可能受到趋化因子受体的调节。

方法

我们通过流式细胞术记录循环 DC 上趋化因子受体的表达，并将 alloHCT 后的发现与急性 GVHD 的发生相关联。

结果

在正常个体中，浆细胞样 DC（pDC）表达高水平的 CCR5，而主要的 CD16 髓样 DC 亚群缺乏 CCR5。然而，其在同种异体混合淋巴细胞反应上清液中的培养诱导了其表达，这一效应主要由干扰素-γ介导。在 42 例 alloHCT 患者中，CD16 DC 上表达了大量 CCR5，而 pDC 上则下调了 CCR5 的表达。移植后任何时候 CCR5CD16 DC 的最大比例与急性 GVHD 相关，而 pDC 上的 CCR5 最小值也显示出类似的相关性。在出现 GVHD 迹象之前，患有 GVHD Ⅱ至Ⅳ级的患者中 CCR5CD16 DC 的最大百分比高于 GVHD 0 级和Ⅰ级的患者，而 GVHD Ⅱ至Ⅳ级的患者中 pDC 上的 CCR5 最小百分比低于 GVHD 0 级和Ⅰ级的患者。CD16 髓样 DC 上的 CCR5 水平超过 20.5％和 CD123 pDC 上的 CCR5 水平低于 22.6％与随后的 GVHD Ⅱ至Ⅳ级具有较高的灵敏度和特异性相关。