Yang H, Yogeeswaran G, Bukowski J F, Welsh R M
Nat Immun Cell Growth Regul. 1985;4(1):21-39.
The sensitivities of mouse natural killer (NK) cells to various antisera and complement were analyzed at different time points after acute lymphocytic choriomeningitis virus infection. Under these conditions NK cell activity peaks 3 days and virus-specific cytotoxic T cell activity 7 days after infection. The sensitivity of the cytotoxic activities to antibodies to asialo GM1 (AGM1), NK 1.2 alloantigen, and Ly 5 was in the order endogenous NK greater than day 3 NK greater than day 7 NK. Day 7 cytotoxic T cells were more resistant than day 7 NK to anti-AGM1 and to anti-NK 1.2, but more sensitive to anti-Ly 5. This decreased sensitivity of activated NK cells to antibodies and C' was examined in more detail for the AGM1 antigen. Antibody to AGM1 completely depleted NK cell activity in control, but not in day 3 lymphocytic choriomeningitis virus infected mice. However, mice treated before infection with antibody did not generate NK cell activity 3 days after infection. The mechanisms of the decreased sensitivity of activated NK cells to antibody to AGM1 was examined. High levels of antibody depleted activity, indicating that the effectors were not devoid of AGM1. Biochemical analyses of spleen leukocytes revealed marked increases in sialic acid, gangliosides, and neutral glycosphingolipids, including AGM1 in the order day 7 greater than day 3 greater than endogenous. Antibody to AGM1 was absorbed out by leukocytes in the order day 7 greater than day 3 greater than endogenous. Flow cytometry (FACS) analyses revealed marked shifts in the frequency and intensity of staining of cells with antibody to AGM1 in the order day 7 greater than day 3 greater than endogenous. All endogenous NK cell activity and all the large granular lymphocytes were associated with the brightest 5% of the total spleen leukocyte population. Day 3 and day 7 NK cell activity was also located in cells sorted by using the gate settings for the top 5% endogenous cells. However, there were marked increases in the number of the very bright cells in the order day 3 greater than day 7 greater than endogenous. These cell numbers correlate with the level of NK cell activity in these fractions. Thus, the decreased sensitivity of activated NK cells to antibody to AGM1 is not due to decreased expression of AGM1 on NK cells, but to a competition for antibody by greatly increased levels of AGM1 in infected spleen leukocytes.(ABSTRACT TRUNCATED AT 400 WORDS)
在急性淋巴细胞性脉络丛脑膜炎病毒感染后的不同时间点，分析了小鼠自然杀伤（NK）细胞对各种抗血清和补体的敏感性。在这些条件下，感染后3天NK细胞活性达到峰值，病毒特异性细胞毒性T细胞活性在感染后7天达到峰值。细胞毒性活性对去唾液酸GM1（AGM1）抗体、NK 1.2同种抗原和Ly 5的敏感性顺序为内源性NK大于感染后3天的NK大于感染后7天的NK。感染后7天的细胞毒性T细胞比感染后7天的NK细胞对抗AGM1和抗NK 1.2更具抗性，但对抗Ly 5更敏感。针对AGM1抗原，更详细地研究了活化的NK细胞对抗体和补体敏感性降低的情况。在对照中，AGM1抗体可完全消除NK细胞活性，但在感染淋巴细胞性脉络丛脑膜炎病毒3天的小鼠中则不能。然而，感染前用抗体处理的小鼠在感染后3天未产生NK细胞活性。研究了活化的NK细胞对AGM1抗体敏感性降低的机制。高水平的抗体可消除活性，表明效应细胞并非缺乏AGM1。对脾白细胞的生化分析显示，唾液酸、神经节苷脂和中性糖鞘脂显著增加，包括AGM1，顺序为感染后7天大于感染后3天大于内源性。AGM1抗体按感染后7天大于感染后3天大于内源性的顺序被白细胞吸收。流式细胞术（FACS）分析显示，用AGM1抗体染色的细胞频率和强度有明显变化，顺序为感染后7天大于感染后3天大于内源性。所有内源性NK细胞活性和所有大颗粒淋巴细胞都与脾白细胞总数中最亮的5%相关。感染后3天和7天的NK细胞活性也位于使用内源性细胞前5%的门控设置分选的细胞中。然而，非常亮的细胞数量有明显增加，顺序为感染后3天大于感染后7天大于内源性。这些细胞数量与这些组分中NK细胞活性水平相关。因此，活化的NK细胞对AGM1抗体敏感性降低并非由于NK细胞上AGM1表达减少，而是由于感染的脾白细胞中AGM1水平大幅增加导致对抗体的竞争。（摘要截断于400字）
