Natural killer (NK) cell stimulatory factor or IL-12 has differential effects on the proliferation of TCR-alpha beta+, TCR-gamma delta+ T lymphocytes, and NK cells.
Natural killer (NK) cell stimulatory factor or IL-12 has differential effects on the proliferation of TCR-alpha beta+, TCR-gamma delta+ T lymphocytes, and NK cells.
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DOI：
10.4049/jimmunol.149.11.3495
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发表时间：
1992-12
影响因子：
4.4
通讯作者：
B. Perussia;S. Chan;Annalisa D'Andrea;K. Tsuji;D. Santoli;M. Pospíšil;D. Young;S. Wolf;Giorgio Trinchieri
中科院分区：
文献类型：
--
作者：
B. Perussia;S. Chan;Annalisa D'Andrea;K. Tsuji;D. Santoli;M. Pospíšil;D. Young;S. Wolf;Giorgio Trinchieri
我们分析了NK细胞刺激因子/IL-12对PBL及其亚群增殖的影响。IL-12与凝集素和磷脂协同作用，诱导CD4+和CD8+外周血T淋巴细胞增殖。在phorpol - di酯诱导增殖的情况下，IL-12的作用部分是由诱导IL-2的产生介导的，正如观察到的那样，IL-12增强了这些培养物中IL-2的产生，而抗IL-2抗体抑制了增殖。IL-12还与抗cd3抗体和同种异体刺激在MLC中协同诱导T细胞增殖。单独IL-12对预激活的T淋巴细胞和NK淋巴细胞有丝分裂作用。在NK淋巴细胞、CD4+和CD8+ tcr - α β +和tcr - γ δ +淋巴细胞上观察到类似剂量的IL-12的有丝分裂作用。在tcr - α - β + T淋巴细胞上，IL-12的作用在很大剂量范围内总是与IL-2的作用叠加。在高度活化、活跃增殖的NK细胞上也观察到同样的效果。然而，在刺激后恢复到静息状态的NK和tcr - γ δ +淋巴细胞以及tcr - γ δ +急性白血病衍生T细胞系上，IL-12显著抑制中至高剂量（10至100 U/ml） IL-2诱导的增殖。这种抑制作用至少部分是间接的，并且依赖于il -12诱导的TNF的产生。中和抗tnf抗体，而不是抗ifn - γ和抗转化生长因子抗体，在这些培养中恢复了超过70%的IL-12诱导的增殖抑制。然而，TNF单独不能模拟IL-12对il -2诱导的NK和tcr - γ δ +淋巴细胞增殖的抑制作用，提示涉及其他机制。这些发现对介导MHC非限制性细胞毒性的淋巴细胞亚群生物学的相关性进行了讨论。
We have analyzed the effects of NK cell stimulatory factor/IL-12, on proliferation of PBL and their subsets. IL-12 synergizes with lectins and phorbol diesters to induce proliferation of CD4+ and CD8+ peripheral blood T lymphocytes. In the case of phorbol-diester-induced proliferation, the effect of IL-12 is in part mediated by induced IL-2 production, as suggested by the observation that IL-12 enhances IL-2 production in these cultures and that anti-IL-2 antibodies inhibit proliferation. IL-12 synergizes also with anti-CD3 antibodies and with allogeneic stimulation in MLC in inducing T cell proliferation. IL-12 alone is mitogenic for preactivated T and NK lymphoblasts. This mitogenic effect is observed with similar doses of IL-12 on NK lymphoblasts as well as on CD4+ and CD8+ TCR-alpha beta+ and on TCR-gamma delta+ lymphoblasts. On TCR-alpha beta+ T lymphocytes the effect of IL-12 is always additive to that of IL-2 over a wide dose range. The same effect is observed on highly activated, actively proliferating NK cells. However, on NK and TCR-gamma delta+ lymphoblasts reverting to a resting state after stimulation and on a TCR-gamma delta+ acute leukemia-derived T cell line, IL-12 inhibits significantly the proliferation induced by moderate to high doses (10 to 100 U/ml) of IL-2. This inhibitory effect is, at least in part, indirect, and depends on IL-12-induced production of TNF. Neutralizing anti-TNF antibodies, but not anti-IFN-gamma and anti-transforming growth factor antibodies, restore by more than 70% the inhibition of proliferation induced by IL-12 in these cultures. However, TNF alone cannot mimic the inhibitory effect of IL-12 on the IL-2-induced proliferation of NK and TCR-gamma delta+ lymphoblasts, suggesting the involvement of additional mechanisms. The relevance of these findings for the biology of lymphocyte subsets mediating MHC nonrestricted cytotoxicity is discussed.