Abrogation of resistance to and enhancement of DLA-nonidentical unrelated marrow grafts in lethally irradiated dogs by thoracic duct lymphocytes.

Abrogation of resistance to and enhancement of DLA-nonidentical unrelated marrow grafts in lethally irradiated dogs by thoracic duct lymphocytes.
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胸导管淋巴细胞对受致命辐射的狗的 DLA 异种无关骨髓移植物的抵抗力被消除并增强。

DOI:
10.1182/blood.v53.4.552.552
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发表时间:
1979
期刊:
影响因子:
20.3
通讯作者:
E. Thomas
E. Thomas
中科院分区:
医学1区
文献类型:
--
作者:
H. Deeg;R. Storb;P. Weiden;H. Shulman;T. Graham;B. Torok;E. Thomas

文献摘要

被引文献

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我们以前曾证明,1200 R全身照射(TBI)后低剂量骨髓(≤ 4 × 108个细胞/kg)移植在DLA-等同中是成功的。但DLA不相同的同窝或无关的狗,提示与主要犬组织相容性复合体(DLA)相关的耐药位点。向骨髓接种物中添加活供体血白细胞始终可以克服耐药性,无论是通过给予增加数量的外周血干细胞,还是通过淋巴细胞介导的作用。体外照射白细胞无效。在当前研究中,8只犬接受1200 R TBI,随后接受来自不相关DLA-不相同供体的2.5 ± 1.4 × 108个骨髓细胞/kg和7.7 ± 3.6 × 108个胸导管淋巴细胞/kg。所有8只犬均表现出迅速和持续的造血植入,无排斥反应。由于犬胸导管淋巴细胞先前已被证明不含造血干细胞,废除犬骨髓移植物的阻力似乎是相关的剩余宿主免疫的积极抑制或增强造血细胞的细胞-细胞相互作用的胸导管淋巴细胞与骨髓细胞。体外研究表明,犬胸导管淋巴细胞与自体骨髓共培养可显著增加红系细胞集落数量,提示后一种机制。
Abstract We have previously shown that grafts with low doses of bone marrow (≤ 4 × 108 cells/kg) after 1200 R total-body irradiation (TBI) are successful in DLA-identical. but not DLA-nonidentical littermate or unrelated dogs, suggesting a locus of resistance associated with the major canine histocompatibility complex (DLA). Addition of viable donor blood leukocytes to the marrow inoculum has consistently overcome resistance, either by administration of an increased number of stem cells from the peripheral blood or through an effect mediated by lymphocytes. In-vitro-irradiated leukocytes have been ineffective. In the current study 8 dogs were given 1200 R TBI followed by 2.5 ± 1.4 × 108 marrow cells/kg and 7.7 ± 3.6 × 108 thoracic duct lymphocytes/kg from unrelated DLA-nonidentical donors. All 8 dogs showed prompt and sustained hemopoietic engraftment, and none rejected. Since canine thoracic duct lymphocytes have previously been shown not to contain hemopoietic stem cells, abrogation of resistance to canine marrow grafts appears to be related either to active suppression of residual host immunity or to enhancement of hemopoiesis by cell-cell interaction of thoracic duct lymphocytes with marrow cells. The latter mechanism is suggested by in vitro studies showing that dog thoracic duct lymphocytes cocultured with autologous marrow significantly increase the number of erythroid colonies.