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原发性人恶性间皮瘤细胞表达II类主要组织相容性复合体、细胞间黏附分子-1和B7-2,并能将回忆抗原呈递给自体血淋巴细胞。

Primary human mesothelioma cells express class II MHC, ICAM-1 and B7-2 and can present recall antigens to autologous blood lymphocytes.

作者信息

Mutti L, Valle M T, Balbi B, Orengo A M, Lazzaro A, Alciato P, Gatti E, Betta P G, Pozzi E

机构信息

S. Maugeri Foundation, Institute for Research and Care, Pavia, Italy.

出版信息

Int J Cancer. 1998 Dec 9;78(6):740-9. doi: 10.1002/(sici)1097-0215(19981209)78:6<740::aid-ijc12>3.0.co;2-5.

Abstract

Mesothelioma cells (MMc) are considered to be weakly immunogenic and the experimental approaches attempting to induce an immune response against these cells have been disappointing. Our aim was to investigate whether MMc possess the surface accessory molecules involved in antigen presentation and whether these cells are capable of presenting recall antigens to autologous blood lymphocytes. Four primary MMc cultures were generated from malignant effusions and examined to assess whether the accessory molecules required for antigen presentation were present on their surfaces. Intercellular adhesion molecule-I (ICAM-I; CD54); class I and class II major histocompatibility complex-DR (MHCI and MHCII-DR); B7-1 (CD80.3); and B7-2 (CD86) expression by MMc was studied by immunocytochemical and/or FACScan analysis. MMc were pulsed with purified protein derivative (PPD), Tetanus toxoid (TT) and Candida albicans (CA) bodies, and incubated with autologous lymphocytes. Lymphocyte proliferation was estimated by radionucleotide incorporation. Phenotypic analysis showed the presence of MHCII-DR, ICAM-I and B7-2 on primary MMc cultures, whereas the phenotypic evaluation of 2 established MMc lines did not show the presence of the B7-1 and B7-2 molecules. In addition, MHCII-DR was detectable only after interferon gamma (IFN-gamma) stimulation. Primary MMc cultures acquired the capability to induce lymphocyte proliferation after pulse with the recall antigens. To achieve characterization of these lymphocytes, we generated a PPD-specific CD4+ T-cell clone. PPD-pulsed MMc were shown to specifically induce T-cell clone proliferation through a MHCII-DR-mediated process. We conclude that primary MMc possess the surface molecules required for antigen presentation and can present recall antigens to CD4+ lymphocytes.

摘要

间皮瘤细胞(MMc)被认为免疫原性较弱,试图诱导针对这些细胞的免疫反应的实验方法一直令人失望。我们的目的是研究MMc是否具有参与抗原呈递的表面辅助分子,以及这些细胞是否能够将回忆抗原呈递给自体血淋巴细胞。从恶性胸腔积液中培养出四种原代MMc,并进行检测以评估抗原呈递所需的辅助分子是否存在于其表面。通过免疫细胞化学和/或流式细胞仪分析研究了MMc上细胞间黏附分子-I(ICAM-I;CD54)、I类和II类主要组织相容性复合体-DR(MHCI和MHCII-DR)、B7-1(CD80.3)和B7-2(CD86)的表达。用纯化蛋白衍生物(PPD)、破伤风类毒素(TT)和白色念珠菌(CA)菌体对MMc进行脉冲处理,并与自体淋巴细胞一起孵育。通过放射性核苷酸掺入法估计淋巴细胞增殖。表型分析显示原代MMc培养物上存在MHCII-DR、ICAM-I和B7-2,而对两个已建立的MMc系的表型评估未显示B7-1和B7-2分子的存在。此外,仅在γ干扰素(IFN-γ)刺激后才可检测到MHCII-DR。原代MMc培养物在用回忆抗原脉冲处理后获得了诱导淋巴细胞增殖的能力。为了对这些淋巴细胞进行表征,我们生成了一个PPD特异性CD4 + T细胞克隆。已证明用PPD脉冲处理的MMc可通过MHCII-DR介导的过程特异性诱导T细胞克隆增殖。我们得出结论,原代MMc具有抗原呈递所需的表面分子,并且可以将回忆抗原呈递给CD4 +淋巴细胞。

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