Dendritic cells stimulate the expansion of bcr-abl specific CD8+ T cells with cytotoxic activity against leukemic cells from patients with chronic myeloid leukemia.
Dendritic cells stimulate the expansion of bcr-abl specific CD8+ T cells with cytotoxic activity against leukemic cells from patients with chronic myeloid leukemia.
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树突状细胞刺激 bcr-abl 特异性 CD8 T 细胞的扩增，对慢性粒细胞白血病患者的白血病细胞具有细胞毒活性。
作者：
M. Nieda;A. Nicol;A. Kikuchi;K. Kashiwase;K. Taylor;Kenji Suzuki;K. Tadokoro;T. Juji
T淋巴细胞在骨髓移植后慢性髓性白血病（CML）控制中的作用已被清楚地证实。这种效应与移植物抗宿主病（GVHD）密切相关。一种与移植物抗白血病（GVL）分离的特异性移植物抗白血病（GVL）效应已被假设，但难以证明。特异性GVL活性的一个可能靶标是CML特征的bcr-abl融合蛋白。我们已经研究了使用正常肽脉冲树突状细胞从正常供体产生细胞毒性，bcr-abl特异性T细胞。T细胞（CD3+, CD8+, TCR α - β +， NK受体阴性）由正常供体（HLA A24, B52, B59, Cw1）刺激后产生，用跨越bcr-abl的b3a2断点的16聚肽引物，裂解来自7例b3a2断点的CML患者外周血的CML细胞。只有b2a2断点的4例CML细胞未被裂解。来源于CML患者外周血的植物血凝素（PHA）原细胞未被裂解，表明细胞毒性不是由于同种异体反应性。抗HLA- a、B、C阻断实验表明，细胞毒性依赖于对主要组织相容性复合体（MHC） I类分子的识别，尽管细胞毒性不受MHC限制，因为并非所有患者都与t细胞供体具有相同的HLA类型。bcr-abl的特异性和无同种异体反应性被证实，对自体和异体I类HLA-A匹配的单核细胞用16个分子量的bcr-abl融合肽脉冲，但对未脉冲的单核细胞或用其他肽脉冲的单核细胞没有裂解活性。这些结果表明，bcr-abl特异性T细胞对CML细胞具有显著的细胞毒性活性，可以从正常供体外周血中产生和扩增。识别HLA分子对细胞毒性是必要的，但严格的HLA身份不是必需的。
The role of T lymphocytes in the control of chronic myeloid leukemia (CML) after bone marrow transplantations has been clearly shown. This effect closely correlates with graft-versus-host disease (GVHD). A specific graft-versus-leukemia (GVL) effect separate from GVHD has been postulated but has been difficult to show. One possible target for specific GVL activity is the bcr-abl fusion protein characteristic of CML. We have investigated the use of normal peptide-pulsed dendritic cells for the generation of cytotoxic, bcr-abl-specific T cells from normal donors. T cells (CD3+, CD8+, TCR alpha beta+, and NK receptor-negative) generated from a normal donor (HLA A24, B52, B59, Cw1) after stimulation with autologous dendritic cells, primed with a 16 mer peptide spanning the b3a2 breakpoint of bcr-abl, lysed CML cells from the peripheral blood of seven patients with CML with the b3a2 breakpoint. CML cells from four patients with only the b2a2 breakpoint were not lysed. Phytohemagglutinin (PHA) blasts derived from peripheral blood of patients with CML were not lysed, suggesting that cytotoxicity was not due to alloreactivity. Blocking experiments with anti-HLA-A,B,C indicated that cytotoxicity was dependent on recognition of major histocompatibility complex (MHC) class I molecules, although cytotoxicity was not MHC-restricted because not all patients shared HLA types with the T-cell donor. Specificity for bcr-abl and absence of alloreactivity was confirmed by the presence of lytic activity against autologous and allogeneic class I HLA-A matched monocytes pulsed with the 16 mer bcr-abl fusion peptide, but not against unpulsed monocytes or monocytes pulsed with other peptides. These results show that bcr-abl-specific T cells with marked cytotoxic activity against CML cells can be generated and amplified from normal donor peripheral blood. Recognition of HLA molecules is essential for cytotoxicity but strict HLA identity is not required.
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影响因子：
20.3
作者：
Bocchia, M;Korontsvit, T;Scheinberg, DA
通讯作者：
Scheinberg, DA
影响因子：
20.3
作者：
Choudhury, A;Gajewski, JL;Champlin, RE
通讯作者：
Champlin, RE
能够选择性破坏带有费城染色体（Ph1）的人类白血病系的同种异体T细胞克隆也可以识别来自同一患者的Ph1-细胞。
影响因子：
20.3
作者：
Oettel,KR;Wesly,OH;Albertini,MR;Hank,JA;Iliopolis,O;Sosman,JA;Voelkerding,K;Wu,SQ;Clark,SS;Sondel,PM
通讯作者：
Sondel,PM
抗黑色素瘤细胞毒性 T 淋巴细胞 (CTL) 识别许多具有“自身”序列的抗原肽：抗黑色素瘤 CTL 反应的自身免疫性质。
影响因子：
4.4
作者：
Tsomides,TJ;Reilly,EB;Eisen,HN
通讯作者：
Eisen,HN
处理并向初始 T 淋巴细胞呈递标称抗原的树突状细胞源自 CD2 前体。
DOI：
--
发表时间：
1997
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Takamizawa,M;Rivas,A;Fagnoni,F;Benike,C;Kosek,J;Hyakawa,H;Engleman,EG
通讯作者：
Engleman,EG