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.
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.
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DOI：
10.3324/haematol.2018.193680
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发表时间：
2019-01
期刊：
影响因子：
10.1
通讯作者：
Jedema I
中科院分区：
文献类型：
--
作者：
Laghmouchi A;Hoogstraten C;van Balen P;Falkenburg JHF;Jedema I
来自10/10的非血缘关系相合的供者的干细胞移植往往与人类白细胞抗原-DP不相合。在一些患者中，针对不匹配的HLADP等位基因的供者T细胞反应(S)被发现在没有发生移植物抗宿主病的情况下诱导了特定的移植物抗白血病效应，而在另一些病例中发生了显著的移植物抗宿主病。异基因人类白细胞抗原特异性供者T细胞谱系识别模式可以解释供者T细胞在人类白细胞抗原不相合异基因干细胞移植后的不同临床效应。为了揭示人类白细胞抗原-DP T细胞谱系的组成，用同种异基因的单核细胞来源的树突状细胞在体外刺激供者T细胞反应。一种包括消除对自体树突状细胞的反应性的策略允许在人类白细胞抗原-DP不匹配的树突状细胞刺激下有效地识别和浓缩同种反应性T细胞。在这项研究中，我们阐明了同种异体的HLA-DP限制性T细胞谱系包含具有不同细胞系特异性识别特征的T细胞。正如预期的那样，一些同种异体的HLA-DP限制性T细胞表现出对多种造血和非造血细胞类型的广泛识别，这些细胞表达靶向错配的HLA-DP等位基因。然而，相当大比例的同种异体HLADP限制性T细胞对造血细胞的识别受到限制，包括原发恶性细胞，甚至只限制识别髓系细胞，包括树突状细胞和原发急性髓系白血病样本，而不识别其他造血细胞和非造血细胞类型。这些数据表明，同种异体的人类白细胞抗原-DP特异性T细胞谱系包含对造血细胞识别受限的T细胞，这可能有助于在不发生移植物抗宿主病的情况下产生特异性的移植物抗白血病效应。
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.
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影响因子：
3.6
作者：
Fleischhauer, Katharina;Beelen, Dietrich W.
通讯作者：
Beelen, Dietrich W.
影响因子：
82.9
作者：
Reddy, P;Maeda, Y;Ferrara, JLM
通讯作者：
Ferrara, JLM
影响因子：
4.8
作者：
Barge, RMY;Starrenburg, CWJ;Willemze, R
通讯作者：
Willemze, R
影响因子：
11.4
作者：
Herr, W.;Eichinger, Y.;Thomas, S.
通讯作者：
Thomas, S.
DOI：
10.1056/nejmoa1500140
发表时间：
2015-08-13
期刊：
The New England journal of medicine
影响因子：
--
作者：
Petersdorf EW;Malkki M;O'hUigin C;Carrington M;Gooley T;Haagenson MD;Horowitz MM;Spellman SR;Wang T;Stevenson P
通讯作者：
Stevenson P