Kanar M C, Thiele D L, Ostensen M, Lipsky P E
Harold C. Simmons Arthritis Research Center, Department of Internal Medicine, University of Texas Health Science Center, Southwestern Medical School, Dallas 75235.
J Clin Immunol. 1988 Jan;8(1):69-79. doi: 10.1007/BF00915159.
Natural killer (NK)-like activity against a renal carcinoma cell line, Cur, was assessed. There was no spontaneous killing of Cur cells by human peripheral blood mononuclear cells in 4-hr assays. Cur killing was observed in 18-hr assays, but the magnitude of killing was variable and always markedly less than that against K562. Cur killing was mediated by a nonadherent, nonphagocytic lymphocyte, the activity of which could be modulated both positively and negatively by monocytes or their products. Preincubation of effectors with monocyte supernatant, interleukin 1 (IL-1), alpha-interferon (alpha IFN), or interleukin 2 (IL-2) greatly increased the magnitude of Cur killing and accelerated the kinetics of lysis. The addition of prostaglandin E2 (PGE2) during in vitro activation of NK by IL-2 profoundly inhibited subsequent Cur lysis, whereas only minimal inhibition of K562 lysis was noted. However, following activation with IL-2, lysis of Cur targets was less sensitive to the inhibitory effects of PGE2. Removal of Leu 11b(+), OKM1(+), or L-leucyl-leucine methyl ester-sensitive cells markedly decreased both Cur and K562 lysis. Moreover, CD16(+) cells purified with the fluorescence-activated cell sorter were found to mediate Cur killing. Whereas Cur and K562 lysis is mediated by phenotypically similar effector cells, the present studies demonstrate that the cytotoxic functions defined by the ability to lyse these two targets differ in response to a variety of immunoregulatory stimuli.
评估了对肾癌细胞系Cur的自然杀伤（NK）样活性。在4小时的检测中，人外周血单个核细胞对Cur细胞没有自发杀伤作用。在18小时的检测中观察到了对Cur细胞的杀伤，但杀伤程度各不相同，且总是明显低于对K562细胞的杀伤。对Cur细胞的杀伤是由一种非黏附、非吞噬性淋巴细胞介导的，单核细胞或其产物可对该淋巴细胞的活性产生正向和负向调节。效应细胞与单核细胞上清液、白细胞介素1（IL-1）、α干扰素（α IFN）或白细胞介素2（IL-2）预孵育，可显著增加对Cur细胞的杀伤程度并加速裂解动力学。在IL-2体外激活NK细胞的过程中添加前列腺素E2（PGE2），可显著抑制随后对Cur细胞的裂解，而对K562细胞裂解的抑制作用则很轻微。然而，在用IL-2激活后，对Cur靶细胞的裂解对PGE2的抑制作用不太敏感。去除Leu 11b(+)、OKM1(+)或L-亮氨酰-亮氨酸甲酯敏感细胞，可显著降低对Cur细胞和K562细胞的裂解。此外，发现用荧光激活细胞分选仪纯化的CD16(+)细胞可介导对Cur细胞的杀伤。虽然对Cur细胞和K562细胞的裂解是由表型相似的效应细胞介导的，但本研究表明，由裂解这两个靶细胞的能力所定义的细胞毒性功能在对多种免疫调节刺激的反应上有所不同。
