Labuda T, Lando P, Björkdahl O, Kalland T, Vessella R, Hedlund G, Eriksson H, Sjögren H O, Dohlsten M
Department of Tumor Immunology, Wallenberg Laboratory, University of Lund, Sweden.
Int Immunol. 1995 Sep;7(9):1425-32. doi: 10.1093/intimm/7.9.1425.
The A6H mAb raised primarily against human renal cell carcinoma (RCC) has previously been shown to bind strongly to RCC, to some degree to colon carcinoma but only marginally to a variety of normal tissues. Immunohistochemical analysis or RCC tissues containing tumor-infiltrating lymphocytes revealed that A6H stained both tumor cells and lymphocytes. FACS analysis of human peripheral blood cells demonstrated that A6H stained both tumor cells and lymphocytes. FACS analysis of human peripheral blood cells demonstrated that A6H mAb stained 85-90% of both CD4+ and CD8+ T cells, but not granulocytes, monocytes, NK cells or B cells. Furthermore, 85-90% of naive and memory T helper cells were stained with A6H suggesting that the A6H mAb defines unique subsets within these T cell populations. Dual staining showed that A6H mAb bind to an antigen that is clearly distinct from other cell surface molecules on T cells, including CD28, CD29, CD26, CD44 and ICAM-2. A6H mAb binding induced a second signal in anti-CD3 mAb activated T cells, resulting in cell proliferation, IL-2 receptor expression and vigorous production of IFN-gamma and TNF, and production of minor amounts of IL-2. Immunoprecipitation with A6H mAb indicated a molecular weight of 120-140 kDa on both T cells and RCC. We suggest that the A6H mAb defines a unique T cell surface antigen which is involved in signal transduction and is expressed on subsets of human T cells. The co-expression of A6H on T cells and tumor cells suggests a possible function related to common properties of these cells.
主要针对人肾细胞癌(RCC)产生的A6H单克隆抗体先前已显示出与肾细胞癌强烈结合,在一定程度上与结肠癌结合,但仅与多种正常组织有微弱结合。对含有肿瘤浸润淋巴细胞的肾细胞癌组织进行免疫组织化学分析显示,A6H可同时染色肿瘤细胞和淋巴细胞。对人外周血细胞进行荧光激活细胞分选(FACS)分析表明,A6H可同时染色肿瘤细胞和淋巴细胞。对人外周血细胞进行FACS分析表明,A6H单克隆抗体可染色85 - 90%的CD4 +和CD8 + T细胞,但不染色粒细胞、单核细胞、自然杀伤(NK)细胞或B细胞。此外,85 - 90%的初始T辅助细胞和记忆T辅助细胞被A6H染色,这表明A6H单克隆抗体定义了这些T细胞群体中的独特亚群。双重染色显示,A6H单克隆抗体与一种明显不同于T细胞上其他细胞表面分子(包括CD28、CD29、CD26、CD44和细胞间黏附分子2(ICAM - 2))的抗原结合。A6H单克隆抗体结合在抗CD3单克隆抗体激活的T细胞中诱导产生第二信号,导致细胞增殖、白细胞介素 - 2(IL - 2)受体表达以及大量产生γ干扰素(IFN - γ)和肿瘤坏死因子(TNF),并产生少量IL - 2。用A6H单克隆抗体进行免疫沉淀表明,在T细胞和肾细胞癌上该分子质量均为120 - 140 kDa。我们认为,A6H单克隆抗体定义了一种独特的T细胞表面抗原,其参与信号转导并在人T细胞亚群上表达。A6H在T细胞和肿瘤细胞上的共表达提示了与这些细胞共同特性相关的一种可能功能。