Balch C M, Tilden A B, Dougherty P A, Cloud G A, Abo T
Surgery. 1984 Jan;95(1):63-70.
p6e monoclonal antibody HNK-1 reacts exclusively with human granular lymphocytes that comprise 16 +/- 1.4% of blood mononuclear cells. In normal individuals, almost all natural killer (NK) and killer (K) cell function resides in this lymphocyte subset. The level of HNK-1+ granular lymphocytes, their stage of differentiation, and NK cell function were examined in 70 colon cancer patients and the results compared with data for 114 age-matched normal individuals. Median levels of granular lymphocytes were significantly depressed in colon cancer patients compared to controls (9% versus 16.5%, P less than 0.0001). Despite the depressed numbers of circulating HNK-1+ cells, NK cell function in the colon cancer patients was essentially the same as in normals (P = 0.78). The HNK-1+ lymphocyte level correlated exactly with NK cell function in about two thirds of normal individuals but only one third of colon cancer patients (P = 0.025). Three possible mechanisms for this dichotomy were examined. First, lymphoid cell subpopulations purified with a fluorescence-activated cell sorter (FACS) were examined for altered NK cell functional activity. HNK-1+ cells from the colon cancer patients exhibited significantly less NK functional activity compared to normals (796 versus 1046 lytic units, P = 0.04). Interestingly, the HNK-1- fraction (predominantly T lymphocytes) had increased NK cell functional activity in the colon cancer patients compared to normals (373 versus 218 lytic units, P = 0.0001). Purified monocytes did not contribute to NK cell functional activity. Second, the functional maturity of the HNK-1+ lymphocytes was correlated with NK activity. Two subsets of HNK-1+ cells were identified by surface membrane markers and purified with the FACS. The more mature HNK-1+ subset (i.e., HNK+Leu-4-M1+) exhibited almost ten times more NK cell functional activity than did the less mature cell fraction (i.e., HNK+Leu-4+M1-) cells in normal individuals (2230 versus 286 lytic units/10(7) cells). Further analysis demonstrated that the ratio of mature to immature HNK+ cells in normal individuals was 3:1, while it was decreased to a 1:1 ratio in colon cancer patients P = 0.005). Third, the influence of prostaglandin-mediated suppression on NK cell activity was examined. PGE2 did not appear to influence NK cell function, since NK cell function was unchanged in vitro in the presence of a prostaglandin synthesis inhibitor.(ABSTRACT TRUNCATED AT 400 WORDS)
p6e单克隆抗体HNK - 1仅与人颗粒淋巴细胞发生反应，这些细胞占血液单核细胞的16±1.4%。在正常个体中，几乎所有的自然杀伤（NK）细胞和杀伤（K）细胞功能都存在于这个淋巴细胞亚群中。对70例结肠癌患者的HNK - 1 +颗粒淋巴细胞水平、分化阶段及NK细胞功能进行了检测，并将结果与114例年龄匹配的正常个体的数据进行了比较。与对照组相比，结肠癌患者颗粒淋巴细胞的中位数水平显著降低（9%对16.5%，P<0.0001）。尽管循环中的HNK - 1 +细胞数量减少，但结肠癌患者的NK细胞功能与正常人基本相同（P = 0.78）。在约三分之二的正常个体中，HNK - 1 +淋巴细胞水平与NK细胞功能完全相关，但在结肠癌患者中只有三分之一（P = 0.025）。研究了造成这种差异的三种可能机制。首先，用荧光激活细胞分选仪（FACS）纯化的淋巴细胞亚群检测NK细胞功能活性的改变。与正常人相比，结肠癌患者的HNK - 1 +细胞表现出明显较低的NK功能活性（796对1046溶细胞单位，P = 0.04）。有趣的是，与正常人相比，结肠癌患者的HNK - 1 -部分（主要是T淋巴细胞）的NK细胞功能活性增加（373对218溶细胞单位，P = 0.0001）。纯化的单核细胞对NK细胞功能活性没有贡献。其次，将HNK - 1 +淋巴细胞的功能成熟度与NK活性相关联。通过表面膜标记物鉴定出HNK - 1 +细胞的两个亚群，并用FACS进行纯化。在正常个体中，较成熟的HNK - 1 +亚群（即HNK + Leu - 4 - M1 +）表现出的NK细胞功能活性几乎是较不成熟细胞部分（即HNK + Leu - 4 + M1 -）细胞的十倍（2230对286溶细胞单位/10⁷细胞）。进一步分析表明，正常个体中成熟与未成熟HNK +细胞的比例为3:1，而在结肠癌患者中该比例降至1:1（P = 0.005）。第三，研究了前列腺素介导的抑制对NK细胞活性的影响。PGE2似乎不影响NK细胞功能，因为在存在前列腺素合成抑制剂的情况下，NK细胞功能在体外没有变化。（摘要截短至400字）
