首页> 美国卫生研究院文献>Haematologica >The allogeneic HLA-DP-restricted T-cell repertoire provoked by allogeneic dendritic cells contains T cells that show restricted recognition of hematopoietic cells including primary malignant cells
【2h】

The allogeneic HLA-DP-restricted T-cell repertoire provoked by allogeneic dendritic cells contains T cells that show restricted recognition of hematopoietic cells including primary malignant cells

机译:由同种树突状细胞激发的同种异体HLA-DP限制的T细胞库包含T细胞这些T细胞显示出对造血细胞(包括原发性恶性细胞)的识别受限

代理获取
本网站仅为用户提供外文OA文献查询和代理获取服务,本网站没有原文。下单后我们将采用程序或人工为您竭诚获取高质量的原文,但由于OA文献来源多样且变更频繁,仍可能出现获取不到、文献不完整或与标题不符等情况,如果获取不到我们将提供退款服务。请知悉。

摘要

Stem cell grafts from 10/10 HLA-matched unrelated donors are often mismatched for HLA-DP. In some patients, donor T-cell responses targeting the mismatched HLA-DP allele(s) have been found to induce a specific graft-versus-leukemia effect without coinciding graft-versus-host disease, whereas in other cases significant graft-versus-host disease occurred. Cell-lineage-specific recognition patterns within the allogeneic HLA-DP-specific donor T-cell repertoire could explain the differential clinical effects mediated by donor T cells after HLA-DP-mismatched allogeneic stem cell transplantation. To unravel the composition of the HLA-DP T-cell repertoire, donor T-cell responses were provoked by in vitro stimulation with allogeneic HLA-DP-mismatched monocyte-derived dendritic cells. A strategy including depletion of reactivity against autologous dendritic cells allowed efficient identification and enrichment of allo-reactive T cells upon stimulation with HLA-DP-mismatched dendritic cells. In this study we elucidated that the allogeneic HLA-DP-restricted T-cell repertoire contained T cells with differential cell-lineage-specific recognition profiles. As expected, some of the allogeneic HLA-DP-restricted T cells showed broad recognition of a variety of hematopoietic and non-hematopoietic cell types expressing the targeted mismatched HLA-DP allele. However, a significant proportion of the allogeneic HLA-DP-restricted T cells showed restricted recognition of hematopoietic cells, including primary malignant cells, or even restricted recognition of only myeloid cells, including dendritic cells and primary acute myeloid leukemia samples, but not of other hematopoietic and non-hematopoietic cell types. These data demonstrate that the allogeneic HLA-DP-specific T-cell repertoire contains T cells that show restricted recognition of hematopoietic cells, which may contribute to the specific graft-versus-leukemia effect without coinciding graft-versus-host disease.
机译:来自10/10 HLA匹配的无关供体的干细胞移植物对于HLA-DP通常不匹配。在某些患者中,发现针对失配的HLA-DP等位基因的供体T细胞反应可诱导特定的移植物抗白血病作用,而不会重合移植物抗宿主病,而在其他情况下,移植物抗宿主病则明显。发生宿主疾病。同种异体HLA-DP特异性供体T细胞库中的细胞谱系特异性识别模式可以解释HLA-DP不匹配的同种异体干细胞移植后由供体T细胞介导的不同临床效果。为了揭示HLA-DP T细胞库的组成,通过用同种异体HLA-DP不匹配的单核细胞衍生的树突状细胞进行体外刺激来激发供体T细胞反应。包括减少对自体树突状细胞的反应性的策略允许在用HLA-DP错配的树突状细胞刺激后有效鉴定和富集同种反应性T细胞。在这项研究中,我们阐明了同种异体HLA-DP限制的T细胞库中包含具有不同细胞谱系特异性识别特征的T细胞。如预期的那样,一些同种异体HLA-DP限制性T细胞显示出广泛表达表达靶向失配HLA-DP等位基因的各种造血和非造血细胞类型。但是,相当一部分异基因HLA-DP限制性T细胞显示出对造血细胞(包括原发性恶性细胞)的识别受到限制,甚至仅对髓样细胞(包括树突状细胞和原发性急性髓性白血病样本)的识别受到限制,造血和非造血细胞类型。这些数据表明,同种异体HLA-DP特异性T细胞库中的T细胞显示出对造血细胞的识别受限,这可能有助于特定的移植物抗白血病作用,而不会导致移植物抗宿主病的发生。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
代理获取

客服邮箱:kefu@zhangqiaokeyan.com

京公网安备:11010802029741号 ICP备案号:京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有
  • 客服微信

  • 服务号