Pinard D, Olsson N O, Chambers W H, Martin F
EPHE: Cancer Immunotherapy Research Laboratory, Faculté de Médecine, Dijon, France.
Cancer Immunol Immunother. 1996 Jan;42(1):15-23. doi: 10.1007/s002620050246.
NKR-P1 has been identified as a triggering structure selectively expressed on rat natural killer (NK) cells and adherent lymphokine-activated killer (A-LAK) cells. In vivo treatment with anti-NKR-P1 monoclonal antibody (mAb 3.2.3) was shown to induce complete inhibition of NK cytotoxicity and elimination of LAK cell precursors in Lewis and Fisher rat strains. We investigated the effects of mAb 3.2.3 in a colon tumor model in BDIX rats. Inoculation of animals with mAb 3.2.3 even at very high doses induced a strong but incomplete inhibition of NK cytotoxicity in nylon-wool-non-adherent spleen and peripheral blood cells. Generation of adherent A-LAK cells from their spleen precursors was also strongly by not fully inhibited. We also investigated the effect of treatment with mAb 3.2.3 on the tumorigenicity of the NK-sensitive REGb cell line. When subcutaneously inoculated in syngeneic animals, REGb cells induce tumors that first grow for 2 weeks, then spontaneously regress and disappear. In contrast with previous results using anti-asialoGM1, no significant difference in tumor growth was observed between rats treated with mAB 3.2.3 and control animals, even with a long-term treatment. In vitro, mAb 3.2.3 exhibited the same incomplete efficiency. Nylon-wool-non-adherent spleen cells treated with mAb 3.2.3 plus complement were completely free of 3.2.3(bright) cells, but retained a substantial NK activity and generated LAK cells after culture with IL-2. After an overnight incubation in standard medium of 3.2.3-depleted spleen cells, 3.2.3(bright) cells were partially recovered and the NK cytotoxic activity, as well as the generation of LAK cells, was significantly enhanced. These results suggest that a strong expression of NKR-P1 is not required for BDIX mononuclear cells to exhibit NK function and generate LAK cells under IL-2 activation.
NKR-P1已被确定为一种触发结构，在大鼠自然杀伤（NK）细胞和贴壁淋巴因子激活的杀伤（A-LAK）细胞上选择性表达。用抗NKR-P1单克隆抗体（mAb 3.2.3）进行体内治疗显示，在Lewis和Fisher大鼠品系中可诱导NK细胞毒性的完全抑制以及LAK细胞前体的消除。我们研究了mAb 3.2.3在BDIX大鼠结肠癌模型中的作用。即使以非常高的剂量给动物接种mAb 3.2.3，也会在尼龙毛非贴壁脾细胞和外周血细胞中诱导NK细胞毒性的强烈但不完全抑制。从其脾前体生成贴壁A-LAK细胞也受到强烈但未完全抑制。我们还研究了用mAb 3.2.3治疗对NK敏感的REGb细胞系致瘤性的影响。当在同基因动物中皮下接种时，REGb细胞诱导的肿瘤首先生长2周，然后自发消退并消失。与先前使用抗去唾液酸GM1的结果相反，即使进行长期治疗，用mAB 3.2.3治疗的大鼠与对照动物之间在肿瘤生长方面未观察到显著差异。在体外，mAb 3.2.3表现出相同的不完全有效性。用mAb 3.2.3加补体处理的尼龙毛非贴壁脾细胞完全没有3.2.3（明亮）细胞，但保留了相当大的NK活性，并且在与IL-2培养后产生LAK细胞。在标准培养基中对去除3.2.3的脾细胞进行过夜孵育后，部分恢复了3.2.3（明亮）细胞，并且NK细胞毒性活性以及LAK细胞的产生均显著增强。这些结果表明，BDIX单核细胞在IL-2激活下表现出NK功能并产生LAK细胞并不需要NKR-P1的强表达。
