Cuturi M C, Murphy M, Costa-Giomi M P, Weinmann R, Perussia B, Trinchieri G
J Exp Med. 1987 Jun 1;165(6):1581-94. doi: 10.1084/jem.165.6.1581.
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.
我们提供的证据表明，不含单核细胞污染的人外周血淋巴细胞在用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），而在用有丝分裂原刺激时产生的TNF水平较低但也很显著。这两种诱导剂优先作用于CD4⁺和CD8⁺的T细胞。自然杀伤细胞（NK细胞）仅在用佛波酯和钙离子载体刺激时产生TNF，且其产生水平远低于T细胞。淋巴细胞纯化过程中所采用的方法以及对各种诱导剂的不同反应能力，使我们能够排除淋巴细胞制剂中污染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）作为单核细胞产生TNF的有效诱导剂，在淋巴细胞制剂中无法诱导出显著水平的TNF。淋巴细胞产生的TNF具有与髓系细胞系或单核细胞经LPS刺激产生的TNF相同的抗原性、物理化学和生化特性。淋巴细胞制剂也能产生淋巴毒素（LT）。对不同诱导剂产生反应时TNF和LT蛋白的产生与细胞质中TNF和LT mRNA的积累是平行的。在mRNA和蛋白质水平上，用佛波酯和钙离子载体刺激T淋巴细胞优先诱导TNF产生，而有丝分裂原刺激则优先诱导LT产生。我们的数据表明，TNF和LT基因这两个紧密相连的基因，编码两种具有几乎相同生物学功能的部分同源蛋白，在淋巴细胞中是独立调控的。
