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首页> 美国卫生研究院文献>The Journal of Clinical Investigation >The effects of chimeric cells following donor bone marrow infusions as detected by PCR-flow assays in kidney transplant recipients.
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The effects of chimeric cells following donor bone marrow infusions as detected by PCR-flow assays in kidney transplant recipients.

机译：PCR流动分析法检测肾移植受体中供体骨髓输注后嵌合细胞的作用。

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40 recipients of first cadaver kidney transplants were given perioperative donor vertebral bone marrow infusions (DBMC), compared with 100 controls who did not receive donor bone marrow. The immunosuppressive regimen included OKT3, Tacrolimus, and steroid maintenance therapy, and, in some patients, newly introduced mycophenolate mofetil. This report describes the 24-mo actuarial follow-up and several immunological monitoring studies including sequential measurements of donor bone marrow lineage subset chimerism by the recently reported PCR-flow assay. This is a sensitive in situ PCR detection system for donor versus recipient histocompatibility genes as well as cell surface CD epitope markers using flow cytometry. The results indicate (a) the stabilization of the donor CD3+ and CD34+ cells in recipient peripheral blood at levels below 1% between 6 mo and 1 yr postoperatively, with a 10-fold higher level of donor cell chimerism of these lineages in recipient iliac crest marrow; (b) significantly lower levels of chimerism in peripheral blood up to 6 mo postoperatively in patients who had early acute (reversible) rejection episodes compared with those who did not; (c) a higher degree of chimerism seen in patients who were class II MHC HLA DR identical with their donors; (d) the identification of a high proportion of the donor bone marrow derived CD3 dimly staining subset of T cells (to which regulatory functions have been ascribed) in recipient peripheral blood and especially in recipient bone marrow; and (e) an unexpectedly increased susceptibility to clinically significant infections (primarily viral), and even death in the DBMC-infused group, compared with controls, but no graft losses because of rejection in the DBMC-infused group. Mixed lymphocyte culture assays showed a trend toward a greater number of nonspecifically low reactors in the DBMC group, as well as a greater number of nonspecifically high reactors in the controls (P = 0.058). The autologous mixed lymphocyte reaction also indicated a trend towards nonspecific immune activation in the DBMC group. Finally, anti-cytomegaloviral IgG antibody reactivity was significantly inhibited in the DBMC group 4-6 mo postoperatively (P = < 0.05). In the controls, there were no donor cell lineages detected by PCR-flow in the peripheral blood. These rather unexpected findings, indicating a more depressed cellular and humoral immune capacity in the DBMC cadaver kidney transplant recipients in this relatively early follow-up period, are discussed relevant to chimerism, MHC restriction, and suppressor activity brought about by specialized DBMC subsets, which still need to be defined.
机译：40名首次尸体肾脏移植接受者接受了围手术期供体椎骨骨髓输注（DBMC），而100名未接受供体骨髓的对照组接受了围手术期。免疫抑制方案包括OKT3，他克莫司和类固醇维持疗法，以及在某些患者中新引入的霉酚酸酯。该报告描述了24个月的精算随访和一些免疫学监测研究，包括通过最近报道的PCR-flow分析法对供体骨髓谱系亚群嵌合体的顺序测量。这是一种使用流式细胞仪检测供体与受体组织相容性基因以及细胞表面CD表位标记的灵敏的原位PCR检测系统。结果表明（a）术后6个月至1年之间，供体外周血中供体CD3 +和CD34 +细胞的稳定水平低于1％，这些谱系在供体中的供体细胞嵌合水平高10倍骨髓; （b）与没有急性早期（可逆）排斥反应的患者相比，术后早期至术后6个月外周血的嵌合水平显着降低； （c）在与供者相同的II类MHC HLA DR患者中发现较高的嵌合率； （d）在受者外周血中，尤其是在受者骨髓中，鉴定出高比例的T细胞供体来源的CD3暗淡染色的T细胞亚群（已赋予调节功能）； （e）与对照组相比，DBMC注入组对临床上显着感染（主要是病毒性感染）的敏感性出乎意料地增加，甚至死亡，但由于DBMC注入组的排斥反应，移植物没有损失。混合淋巴细胞培养分析表明，DBMC组中有更多的非特异性低反应器，而对照组中有更多的非特异性高反应器（P = 0.058）。自体混合淋巴细胞反应也表明DBMC组有非特异性免疫激活的趋势。最后，DBMC组术后4-6 mo明显抑制了抗巨细胞病毒IgG抗体的反应性（P = <0.05）。在对照中，在外周血中没有通过PCR流检测到供体细胞谱系。这些相当出乎意料的发现表明，在相对早期的随访期内，DBMC尸体肾脏移植受者的细胞和体液免疫能力下降，这些与嵌合，MHC限制和特定DBMC亚群带来的抑制活性有关。仍然需要定义。

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