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来自裸鼠的化学诱导肉瘤比来自同基因正常小鼠的相似肉瘤具有更强的免疫原性。

Chemically induced sarcomas from nude mice are more immunogenic than similar sarcomas from congenic normal mice.

作者信息

Svane I M, Engel A M, Nielsen M B, Ljunggren H G, Rygaard J, Werdelin O

机构信息

Institute for Medical Microbiology and Immunology, University of Copenhagen, Denmark.

出版信息

Eur J Immunol. 1996 Aug;26(8):1844-50. doi: 10.1002/eji.1830260827.

Abstract

To detect possible differences in immunogenicity between tumors induced in T cell-deficient mice and phenotypically normal congenic mice, 16 sarcomas, 8 having developed in nude BALB/c mice and 8 having developed in congenic normal (nu/+) mice, were transplanted to normal BALB/c recipients and the rates of rejection or acceptance were registered. The 16 tumors were chosen randomly from a panel of 39 sarcomas induced with 0.5% or 0.1% 3-methylcholanthrene and maintained as cell lines in culture. Out of the tumors originating from nude mice, 66% were rejected by the normal BALB/c recipients, while only 30% of the tumors originating from normal mice were rejected. Tumors with short induction times from normal mice were more readily accepted than tumors with long induction times. Tumors originating from nude mice had significantly longer mean latency times after transplantation to both normal and nude recipients than tumors originating from normal mice. Contrary to what has been reported by others, there was no correlation between the rejection rates of the individual tumors and their Kd, Dd or Ld major histocompatibility complex (MHC) class I surface expression as measured by flow cytometric analysis of cultured tumor cells. The Kd, Dd and Ld proteins of the transplanted tumor lines were analyzed by isoelectric focusing for the occurrence of mutations resulting in altered charge of the MHC protein. No such mutations were found, ruling out MHC mutations of that kind as the source of immunogenicity in the cell lines used in these experiments. Our results suggest the existence of a T cell-mediated selection in the original tumor cell mass of tumors induced in normal mice, adapting the tumor to growth in a host with a functional T cell system, but apparently there is no connection between this loss of immunogenicity and loss of MHC class I expression.

摘要

为检测T细胞缺陷小鼠诱导产生的肿瘤与表型正常的同基因小鼠诱导产生的肿瘤在免疫原性上的可能差异,将16个肉瘤(8个在裸BALB/c小鼠中形成,8个在同基因正常(nu/+)小鼠中形成)移植到正常BALB/c受体小鼠体内,并记录排斥或接受率。这16个肿瘤是从用0.5%或0.1% 3-甲基胆蒽诱导产生并在培养中维持为细胞系的39个肉瘤中随机选取的。源自裸鼠的肿瘤中,66%被正常BALB/c受体小鼠排斥,而源自正常小鼠的肿瘤只有30%被排斥。诱导时间短的正常小鼠肿瘤比诱导时间长的肿瘤更容易被接受。源自裸鼠的肿瘤移植到正常和裸受体小鼠后,其平均潜伏期明显长于源自正常小鼠的肿瘤。与其他人的报道相反,通过对培养的肿瘤细胞进行流式细胞术分析测量,单个肿瘤的排斥率与其Kd、Dd或Ld主要组织相容性复合体(MHC)I类表面表达之间没有相关性。通过等电聚焦分析移植肿瘤系的Kd、Dd和Ld蛋白,以检测是否发生导致MHC蛋白电荷改变的突变。未发现此类突变,排除了这类MHC突变是这些实验中所用细胞系免疫原性来源的可能性。我们的结果表明,在正常小鼠诱导产生的肿瘤的原始肿瘤细胞群中存在T细胞介导的选择,使肿瘤适应在具有功能性T细胞系统的宿主中生长,但显然这种免疫原性的丧失与MHC I类表达的丧失之间没有联系。

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