Host resistance directed selectively against H-2-deficient lymphoma variants. Analysis of the mechanism.
Host resistance directed selectively against H-2-deficient lymphoma variants. Analysis of the mechanism.
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DOI：
10.1084/jem.162.6.1745
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发表时间：
1985-12-01
期刊：
影响因子：
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通讯作者：
Kärre K
中科院分区：
文献类型：
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作者：
Ljunggren HG;Kärre K
从C57BL/6小鼠来源的RBL-5和EL-4 T淋巴瘤中选择了三个细胞表面H-2显著减少的独立变异体。在同基因小鼠皮下接种低剂量细胞后，H-2变异体未能生长，而H-2+对照品系显示出渐进性生长。在组织培养中，生长速度和克隆效率没有明显差异。详细分析了其中一株H-2-Low株体内肿瘤生长的差异。将H-2低变异体和对照品系注射到同一只小鼠的两侧皮下后，生长差异仍然存在，而且不依赖于成熟T细胞的活性，因为在裸鼠身上也看到了同样的结果。这种差异对寄主的辐射部分敏感。当用抗asialo GM1抗血清(已知可抑制自然杀伤(NK)细胞活性)预处理小鼠时，突起的差异被消除，对照品系和H-2变异体在体内都显示出进行性生长。比较同位素标记的变异细胞和野生型细胞的分布和存活的实验表明，前者在静脉注射后24小时内迅速消除。在用抗asialo GM1抗血清治疗的小鼠中，没有发现这些肿瘤消除方面的差异。我们得出结论，H-2表达受损的亚系的致瘤性降低很大程度上(如果不是完全)是由于NK细胞的快速消除。这些发现可能反映了控制H-2表达的因素和NK敏感性之间的反向间接关系。另一种可能的解释是，主要组织相容性复合体(MHC)编码的基因产物直接参与NK细胞系统中的调节信号。根据这一解释，NK细胞系统中的免疫选择性将通过未能识别自身MHC而实现，无论是否存在外来抗原，即通过检测无我而不是非我。这也可以解释以前观察到的H-2连锁杂交抵抗淋巴样移植物以及与肿瘤进展相关的H-2表型的变化。
Three independent variants with a profound reduction of cell surface H- 2 have been selected from the C57BL/6 mouse-derived RBL-5 and EL-4 T lymphomas. After subcutaneous inoculation of low cell doses in syngeneic mice, the H-2- variants failed to grow out, whereas the H-2+ control lines showed progressive growth. No difference in growth rate or cloning efficiency was detectable in tissue culture. The in vivo difference in tumor outgrowth was analyzed in detail for one of the H-2- low lines. The outgrowth difference remained after the H-2-low variant and the control line had been injected subcutaneously in opposite flanks of the same mouse, and it was not dependent upon activity of mature T cells, since the same result was seen in athymic nude mice. The difference was partially sensitive to irradiation of the hosts. When mice were pretreated with anti-asialo GM1 antiserum, known to depress natural killer (NK) cell activity, the difference in outgrowth was abolished, and both the control line and the H-2- variant showed progressive growth in vivo. Experiments comparing the distribution and survival of isotope-prelabeled variant and wild type cells indicated that a rapid elimination of the former took place within 24 h after intravenous injection. These differences in tumor elimination were not seen in mice treated with anti-asialo GM1 antiserum. We conclude that the reduced tumorigenicity of sublines with impaired H-2 expression is largely, if not exclusively due to rapid elimination by NK cells. These findings may reflect an inverse, indirect relation between factors controlling H-2 expression and NK sensitivity. Another possible explanation is that major histocompatibility complex (MHC)-encoded gene products are directly involved in a regulatory signal in the NK cell system. According to this interpretation, immunological selectivity in the NK cell system would be achieved by the failure to recognize self- MHC, irrespective of the presence of foreign antigens, i.e. by detection of no-self rather than of nonself. This may also explain previous observations on H-2-linked hybrid resistance against lymphoid grafts and changes in H-2 phenotypes associated with tumor progression.