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H-2Kb基因转染对B16黑色素瘤细胞转移能力的免疫和非免疫影响

Immunological and non-immunological influence of H-2Kb gene transfection on the metastatic ability of B16 melanoma cells.

作者信息

De Giovanni C, Palmieri G, Nicoletti G, Landuzzi L, Scotlandi K, Bontadini A, Tazzari P L, Sensi M, Santoni A, Nanni P

机构信息

Istituto di Cancerologia, Università di Bologna, Italy.

出版信息

Int J Cancer. 1991 May 10;48(2):270-6. doi: 10.1002/ijc.2910480220.

Abstract

The H-2b-negative B78HI clone (derived from B16 melanoma) was transfected with the H-2Kb gene; 4 cell clones expressing membrane H-2Kb antigens and 2 control clones (transfected with pSV2neo alone) were used for studies of metastatic ability, immunogenicity, NK sensitivity and homotypic adhesion. The experimental metastatic capacity of H-2Kb transfectants in syngenic mice was greatly diminished in comparison with control and parent cells. Both immune-mediated and intrinsic properties of transfectants correlated with their lower metastatic ability. A cell-mediated cytotoxic response was induced by repeated in vivo immunizations of syngeneic mice followed by in vitro restimulation of effectors when transfectants (but not controls) were used as immunizers and as targets. Moreover, homotypic adhesion of H-2Kb transfectants was significantly lower than that of controls. Sensitivity to NK cells of transfectants was not decreased in comparison to H-2-negative controls. It is known that in vitro treatment with IFN-gamma of H-2-positive B16 melanoma cells induces a simultaneous increase in H-2 expression and in experimental metastasis; treatment of H-2Kb transfectants with IFN-gamma induced a higher Kb expression, but no increase in metastatic ability, thus suggesting that the IFN-sensitive component that mediates enhancement of metastasis is not H-2Kb.

摘要

将H-2Kb基因转染至H-2b阴性的B78HI克隆(源自B16黑色素瘤);使用4个表达膜H-2Kb抗原的细胞克隆和2个对照克隆(仅用pSV2neo转染)来研究转移能力、免疫原性、NK敏感性和同型黏附。与对照细胞和亲本细胞相比,H-2Kb转染子在同基因小鼠中的实验转移能力大大降低。转染子的免疫介导特性和内在特性均与其较低的转移能力相关。当使用转染子(而非对照)作为免疫原和靶标时,同基因小鼠经反复体内免疫,随后效应细胞进行体外再刺激,可诱导细胞介导的细胞毒性反应。此外,H-2Kb转染子的同型黏附明显低于对照。与H-2阴性对照相比,转染子对NK细胞的敏感性并未降低。已知用IFN-γ体外处理H-2阳性的B16黑色素瘤细胞会同时导致H-2表达增加和实验性转移增加;用IFN-γ处理H-2Kb转染子可诱导更高的Kb表达,但转移能力并未增加,因此表明介导转移增强的IFN敏感成分不是H-2Kb。

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