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用流感病毒血凝素或小鼠白细胞介素-2基因转染的不表达I类主要组织相容性复合体的小鼠肿瘤的免疫原性

Immunogenicity of a non-class I MHC expressing murine tumor transfected with the influenza virus hemagglutinin or murine interleukin-2 genes.

作者信息

Itaya T, Fearon E, Fiesinger T, Hunt B, Vogelstein B, Frost P

机构信息

Department of Cell Biology, University of Texas M.D. Anderson Cancer Center, Houston 77030.

出版信息

Cancer Immunol Immunother. 1991;33(4):267-73. doi: 10.1007/BF01744947.

Abstract

The transfection of murine SP1 tumor cells with the hemagglutinin (HA) gene of influenza virus results, after fluorescent-activated cell sorting (FACS), in the selection of high-HA-expressing cell lines called H4A and H4B. Both lines fail to grow in syngeneic animals at doses that result in 100% tumor take of non-transfected tumor cells. Both grow in immunosuppressed mice. SP1 and H4A or H4B cells express few class I major histocompatibility complex (MHC) antigens but do express class II IAk antigens. H4A or H4B cells engender a cytotoxic T lymphocyte (CTL) response but cannot protect against a challenge with SP1 cells. This CTL response is inhibited by anti-CD4 but not anti-CD8 antibodies. Using FACS, we were able to select a population (called H5AK5) with high class-I MHC antigen expression. Like H4A and H4B, H5AK5 cells fail to grow in syngeneic animals but do grow in immunosuppressed mice. However, unlike H4A or H4B, H5AK5 can induce protection against a challenge with 1 x 10(5) SP1 cells. These studies indicate that the immunogenicity of HA-transfected SP1 cells may correlate with the cell-surface expression of class II MHC antigens. However, HA-expressing SP1 cells seem able to induce a protective response against a parent SP1 cell challenge only if they also express class I MHC antigens. This view is supported by the observations that SP1 cells expressing murine interleukin-2 do not express class I MHC antigens, fail to grow in syngeneic animals, do grow in immunosuppressed mice but do not protect against a challenge with parental SP1 cells.

摘要

用流感病毒的血凝素(HA)基因转染小鼠SP1肿瘤细胞,经荧光激活细胞分选(FACS)后,可筛选出高表达HA的细胞系,称为H4A和H4B。在同基因动物中,以能使未转染肿瘤细胞100%成瘤的剂量接种这两种细胞系,它们均无法生长。但在免疫抑制小鼠中,它们都能生长。SP1以及H4A或H4B细胞表达很少的I类主要组织相容性复合体(MHC)抗原,但确实表达II类IAk抗原。H4A或H4B细胞能引发细胞毒性T淋巴细胞(CTL)反应,但不能抵御SP1细胞的攻击。这种CTL反应可被抗CD4抗体而非抗CD8抗体抑制。利用FACS,我们能够筛选出一个高表达I类MHC抗原的群体(称为H5AK5)。与H4A和H4B一样,H5AK5细胞在同基因动物中无法生长,但在免疫抑制小鼠中能生长。然而,与H4A或H4B不同的是,H5AK5能诱导抵御1×10⁵个SP1细胞攻击的保护作用。这些研究表明,HA转染的SP1细胞的免疫原性可能与II类MHC抗原的细胞表面表达相关。然而,表达HA的SP1细胞似乎只有在同时表达I类MHC抗原时,才能诱导针对亲本SP1细胞攻击的保护性反应。这一观点得到以下观察结果的支持:表达小鼠白细胞介素-2的SP1细胞不表达I类MHC抗原,在同基因动物中无法生长,在免疫抑制小鼠中能生长,但不能抵御亲本SP1细胞的攻击。

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