Independent regulation of tumor necrosis factor and lymphotoxin production by human peripheral blood lymphocytes.
Independent regulation of tumor necrosis factor and lymphotoxin production by human peripheral blood lymphocytes.
复制标题
人类外周血淋巴细胞对肿瘤坏死因子和淋巴毒素产生的独立调节。
DOI：
10.1084/jem.165.6.1581
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发表时间：
1987-06-01
影响因子：
15.3
通讯作者：
Trinchieri, G
中科院分区：
文献类型：
--
作者：
Cuturi, M C;Murphy, M;Costa-Giomi, M P;Weinmann, R;Perussia, B;Trinchieri, G
我们提供的证据表明，无单核细胞污染的人外周血淋巴细胞在受到佛波酯和钙离子载体刺激时能迅速产生高水平的肿瘤坏死因子（TNF），在受到有丝分裂原刺激时也能产生较低但仍显著水平的TNF。这两类诱导剂优先作用于T细胞，包括CD4⁺和CD8⁺ T细胞。自然杀伤（NK）细胞仅在受到佛波酯和钙离子载体刺激时才产生TNF，且其产生水平远低于T细胞。淋巴细胞纯化过程以及对不同诱导剂反应的差异能力使我们能够排除污染淋巴细胞制剂的单核细胞或嗜碱性粒细胞参与TNF的产生。特别是，脂多糖（LPS）是一种能有效诱导单核细胞产生TNF的物质，但它无法在淋巴细胞制剂中诱导出显著水平的TNF。淋巴细胞产生的TNF在抗原性、物理化学和生物化学特性上与髓系细胞系或单核细胞受LPS刺激后产生的TNF相同。淋巴毒素（LT）也可由淋巴细胞制剂产生。针对不同诱导剂产生TNF和LT蛋白的过程与细胞质中TNF和LT mRNA的积累是平行的。在mRNA和蛋白质水平上，佛波酯和钙离子载体刺激T淋巴细胞优先诱导TNF的产生，而有丝分裂原刺激则优先诱导LT的产生。我们的数据表明，TNF和LT基因这两个紧密连锁的基因编码两种部分同源且生物学功能几乎相同的蛋白质，它们在淋巴细胞中是独立调控的。
We present evidence that human peripheral blood lymphocytes, free of contaminating monocytes, rapidly produce high levels of tumor necrosis factor (TNF) when stimulated with phorbol diester and calcium ionophore, and lower but significant levels of TNF when stimulated with mitogens. These two types of inducers act preferentially on T cells, both CD4+ and CD8+. NK cells produce TNF only when stimulated with phorbol diester and calcium ionophore, and they do so at a much lower level than T cells. The procedures used in the purification of lymphocytes and the differential ability to respond to various inducers allow us to exclude that monocytes or basophils contaminating the lymphocyte preparation participate in the production of TNF. In particular, LPS, a potent inducer of TNF production from monocytes, is unable to induce significant levels of TNF in the lymphocyte preparations. The TNF produced by lymphocytes has antigenic, physicochemical, and biochemical characteristics identical to those of the TNF produced by myeloid cell lines or monocytes upon stimulation with LPS. LT is also produced by lymphocyte preparations. Production of TNF and LT proteins in response to the different inducers is paralleled by accumulation of cytoplasmic TNF and LT mRNA. Both at mRNA and at protein levels, stimulation of T lymphocytes with phorbol diester and calcium ionophore preferentially induces TNF, whereas mitogen stimulation preferentially induces LT. Our data suggest that the TNF and LT genes, two closely linked genes encoding two partially homologous proteins with almost identical biological functions, are independently regulated in lymphocytes.