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首页> 外文期刊>The Journal of Experomental Medicine >Minor histocompatibility antigen-specific cytotoxic T cell lines, capable of lysing human hematopoietic progenitor cells, can be generated in vitro by stimulation with HLA-identical bone marrow cells.
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Minor histocompatibility antigen-specific cytotoxic T cell lines, capable of lysing human hematopoietic progenitor cells, can be generated in vitro by stimulation with HLA-identical bone marrow cells.

机译:能够裂解人类造血祖细胞的次要组织相容性抗原特异性细胞毒性T细胞系可通过与HLA相同的骨髓细胞刺激而在体外产生。

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摘要

Recipient-antidonor alloreactivity before HLA genotypically identical bone marrow transplantation (BMT) between donor-recipient pairs that are negative in the mixed lymphocyte reaction (MLR), the cell-mediated lympholysis (CML) assay, and the lymphocyte crossmatch was not detectable in the majority of cases, using recipient peripheral blood lymphocytes (PBL) collected before BMT as responder cells and donor PBL as stimulator cells. However, when donor bone marrow mononuclear cells (BMMNC) instead of PBL were used as stimulator cells, we could detect donor-specific alloreactivity in 7 of 10 HLA genotypically identical donor-recipient pairs. To demonstrate that this alloreactivity was minor histocompatibility (mH) antigen specific and not directed against HLA class I splits or variants, two cytotoxic T lymphocyte (CTL) lines were tested in further detail against phytohemagglutinin (PHA) blasts from pairs of HLA genotypically identical siblings positive for the HLA class I restriction molecule. Both CTL lines recognized mH antigens, as illustrated by the differential recognition of PHA blasts of one of the two siblings from several pairs. The potential role of these mH antigen-specific CTLs in bone marrow graft rejection was demonstrated by the mH antigen-specific growth inhibition of hematopoietic progenitor cells from the original bone marrow donor and from HLA class I restriction molecule-positive individuals who expressed the mH antigens on their PBL and BMMNC. Our assay can be used in HLA genotypically identical BMT to detect a recipient-antidonor response, directed against cellularly defined mH antigens expressed on donor HPC, BMMNC, and PBL, before transplantation.
机译:在混合淋巴细胞反应(MLR),细胞介导的淋巴分解(CML)分析为阴性的供体-受体对之间在HLA基因型相同的骨髓移植(BMT)之间,受体-供体的同种异体反应在淋巴细胞中不能检测到。大多数情况下,使用在BMT之前收集的受体外周血淋巴细胞(PBL)作为应答细胞,并使用供体PBL作为刺激细胞。但是,当使用供体骨髓单核细胞(BMMNC)代替PBL作为刺激细胞时,我们可以在基因型相同的10个HLA供体-受体对中的7个中检测到供体特异性同种异体反应。为了证明这种同种异体反应是次要的组织相容性(mH)抗原特异性的,并且不针对HLA I类分裂或变体,针对来自HLA基因型相同的同胞对的植物血凝素(PHA)胚芽进一步测试了两个细胞毒性T淋巴细胞(CTL)系HLA I类限制分子呈阳性。两条CTL品系均识别mH抗原,如对来自几对的两个同胞之一的PHA母细胞的差异识别。这些mH抗原特异性CTL在骨髓移植排斥反应中的潜在作用已通过原始骨髓供体和表达mH抗原的HLA I类限制性分子阳性个体对造血祖细胞的mH抗原特异性生长抑制而得到证实。在其PBL和BMMNC上。我们的测定可用于HLA基因型相同的BMT,以检测受体-抗体应答,该应答针对移植前在供体HPC,BMMNC和PBL上表达的细胞定义的mH抗原。

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