HLA identical leukemia cells and T cell growth factor activate cytotoxic T cell recognition of minor locus histocompatibility antigens in vitro.
HLA identical leukemia cells and T cell growth factor activate cytotoxic T cell recognition of minor locus histocompatibility antigens in vitro.
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HLA 相同的白血病细胞和 T 细胞生长因子在体外激活细胞毒性 T 细胞对次要位点组织相容性抗原的识别。
DOI：
10.1172/jci110933
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发表时间：
1983
期刊：
影响因子：
--
通讯作者：
Bozdech,MJ
中科院分区：
文献类型：
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作者：
Sondel,PM;Hank,JA;Wendel,T;Flynn,B;Bozdech,MJ
来自一位健康的人类白细胞抗原相合的骨髓移植供者的淋巴细胞在体外被测试了它们摧毁她哥哥的急性髓系白血病母细胞的能力。患者缓解期(移植前)和供者淋巴细胞的原代混合淋巴细胞培养(MLC)和细胞介导的裂解(CML)反应均为阴性。用照射的白血病细胞、白血病细胞加同种异体照射的淋巴细胞或来自10个供者的照射淋巴细胞池体外刺激供者淋巴细胞7d，不能激活任何能够破坏人类白细胞抗原相合的白血病细胞的细胞毒细胞。进一步培养7d后，T细胞生长因子(TCGF)产生的淋巴细胞对白血病母细胞具有有效的细胞毒作用，但对自体淋巴细胞无明显杀伤作用。只有在最初用照射的白血病细胞刺激的培养中才能观察到对白血病的有效杀伤。这些细胞毒细胞维持在TCGF中，并介导对白血病靶细胞的持续杀伤。他们还能够摧毁患者父母的淋巴细胞，但不能摧毁无关细胞捐赠者的淋巴细胞。这提示了对患者遗传的非人类白细胞抗原的特异性识别，这些非人类白细胞抗原是人类白细胞抗原相合的骨髓供者所不具备的。这些淋巴细胞是通过有限稀释技术克隆的，其中一个克隆对AML原始细胞和父亲的淋巴细胞保持细胞毒性，但对母亲或HLA相合捐赠者的淋巴细胞没有细胞毒性。这种细胞毒性可被抗人类白细胞抗原的单抗抑制。因此，用AML细胞体外致敏这位兄弟姐妹的淋巴细胞，然后进行TCGF扩增和克隆，能够检测到识别微小基因座组织相容抗原的人类白细胞抗原限制性细胞毒细胞。这种免疫识别可能与在白血病动物和组织相容造血移植后的患者中观察到的“移植物对白血病”效应有关。
Lymphocytes from a healthy HLA-identical bone marrow transplant donor were tested for their ability to destroy her brother's acute myelogenous leukemia blasts in vitro. Primary mixed lymphocyte culture (MLC) and cell-mediated lysis (CML) responses between the patient's remission (pretransplant) and donor's lymphocytes were negative. Stimulation of donor lymphocytes for 7 d in vitro with irradiated leukemia cells, leukemia cells plus allogeneic irradiated lymphocytes, or a pool of irradiated lymphocytes from 10 donors, did not activate any cytotoxic cells able to destroy the HLA identical leukemic blasts. Further culturing for 7 additional d in T cell growth factor (TCGF) generated lymphocytes that induced effective cytotoxicity against the leukemic blasts, but not against autologous lymphocytes. Effective killing against the leukemia was observed only in cultures initially stimulated with the irradiated leukemia cells. These cytotoxic cells were maintained in TCGF and mediated persistent killing against the leukemic target cells. They were also able to destroy lymphocytes from the patient's mother and father, but not from an unrelated cell donor. This suggested specific recognition of non-HLA antigens inherited by the patient, that were foreign to the HLA identical bone marrow donor. These lymphocytes were cloned by a limiting dilution technique and one clone maintained cytotoxicity to the AML blasts and the father's lymphocytes, but not lymphocytes from the mother or an HLA-identical donor. This cytotoxicity was inhibited by a monoclonal anti-HLA antibody. Thus, in vitro sensitization of this sibling's lymphocytes with AML blasts followed by TCGF expansion, and cloning, enabled the detection of HLA-restricted cytotoxic cells that recognize minor locus histocompatibility antigens. This immune recognition may be relevant to the "graft vs. leukemia" effect that has been observed in leukemic animals and patients following histocompatible hematopoietic transplants.