首页> 外文期刊>Nature >Spontaneous resistance to acute T-cell leukaemias in TCRV gamma 1.1J gamma 4C gamma 4 transgenic mice.
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Spontaneous resistance to acute T-cell leukaemias in TCRV gamma 1.1J gamma 4C gamma 4 transgenic mice.

机译:在TCRVγ1.1Jγ4Cγ4转基因小鼠中对急性T细胞白血病的自发耐药性。

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The concept of tumour surveillance implies that specific and non-specific components of the immune system eliminate tumours in the early phase of malignancy. The immunological mechanisms that control growth of preneoplastic cells are, however, not known. T cells expressing gamma delta T-cell receptors (TCR) were first described as lymphocytes with reactivity against various tumour cells, which suggests that gamma delta T cells could mediate tumour surveillance. Here we show that TCRV gamma 1.1J gamma 4C gamma 4 transgenic mice are spontaneously resistant to acute T-cell leukaemias but cannot reject non-haematopoietic tumours. TCRV gamma 1.1J gamma 4C gamma 4+ hybridomas isolated from these mice react in vitro against almost all haematopoietic tumour cell lines tested. Recognition of tumour cells depends on the gamma delta TCR but is independent of major histocompatibility complex (MHC) class I, MHC class II, or TAP-2 peptide transporter expression. Ligand recognition is influenced by the murine Nromp gene, which confers resistance or susceptibility to tuberculosis, lepra and leishmaniasis. These data indicate that TCRV gamma 1.1+ T cells confer spontaneous immunity against haematopoietic tumours in vivo and link innate resistance to bacterial infections with tissue-specific tumour surveillance by gamma delta+ T cells.
机译:肿瘤监视的概念意味着免疫系统的特异性和非特异性成分可以在恶性肿瘤的早期消除肿瘤。然而,控制前肿瘤细胞生长的免疫机制尚不清楚。表达γ-δT细胞受体(TCR)的T细胞首先被描述为对各种肿瘤细胞具有反应性的淋巴细胞,这表明γ-δT细胞可以介导肿瘤的监测。在这里,我们显示TCRV伽玛1.1J伽玛4C伽玛4转基因小鼠对急性T细胞白血病具有自发性抵抗力,但不能排斥非造血肿瘤。从这些小鼠中分离出的TCRVγ1.1Jγ4Cγ4+杂交瘤体外对几乎所有测试的造血肿瘤细胞系产生反应。肿瘤细胞的识别取决于伽马三角洲TCR,但独立于主要的组织相容性复合体(MHC)I类,MHC II类或TAP-2肽转运蛋白表达。配体识别受到鼠Nromp基因的影响,该基因赋予对结核病,麻风病和利什曼病的抵抗力或敏感性。这些数据表明,TCRVγ1.1+ T细胞在体内赋予了针对造血肿瘤的自发免疫力,并将对细菌感染的先天性抵抗力与γ-δ+ T细胞对组织特异性肿瘤的监测联系起来。

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