Bakhiet M, Mix E, Kristensson K, Wigzell H, Olsson T
Department of Neurology, Huddinge University Hospital, Karolinska Institute, Stockholm Sweden.
Eur J Immunol. 1993 Jul;23(7):1535-9. doi: 10.1002/eji.1830230721.
Trypanosoma brucei brucei releases a lymphocyte-triggering factor (TLTF) that activates CD8+ T cells. We here study second messenger mechanisms in this activation, i.e. the effects of protein kinase C (PKC), protein kinase A (PKA) and tyrosine kinases (TPK) inhibitors on TLTF-induced interferon-gamma (IFN-gamma) secretion and proliferation in lymphoid cell cultures. The effects were compared to those obtained by phytohemagglutinin (PHA) stimulation. Rat spleen mononuclear cells (MNC) and spleen MNC from a mutant mouse strain possessing CD8+ T cells but lacking CD4+ T cells were used as responder cells. Although both the PKC and the PKA inhibitors suppressed PHA-induced IFN-gamma secretion and proliferation of rat MNC and mouse CD8+ CD4- MNC, they had no effect on the same TLTF-induced responses. The TPK inhibitor genistein, however, strongly suppressed TLTF-induced activation of both types of responder cells to IFN-gamma secretion and the TLTF-induced proliferation of mouse CD8+ CD4- MNC. The suppressive effects of the drugs could be overcome by ionomycin and tetradecanoylphorbol acetate, which show that the effects were not due to drug nonspecific cellular toxicity of the drugs. We conclude that TLTF activates CD8+ T cells through pathways other than the PKC- or PKA-dependent signal transduction, and that TPK may be involved in the triggering.
布氏布氏锥虫释放一种淋巴细胞触发因子（TLTF），该因子可激活CD8⁺T细胞。我们在此研究这种激活过程中的第二信使机制，即蛋白激酶C（PKC）、蛋白激酶A（PKA）和酪氨酸激酶（TPK）抑制剂对TLTF诱导的淋巴细胞培养物中γ干扰素（IFN-γ）分泌和增殖的影响。将这些影响与通过植物血凝素（PHA）刺激获得的影响进行比较。来自具有CD8⁺T细胞但缺乏CD4⁺T细胞的突变小鼠品系的大鼠脾单核细胞（MNC）和脾MNC用作反应细胞。尽管PKC和PKA抑制剂均抑制了PHA诱导的大鼠MNC和小鼠CD8⁺CD4⁻MNC的IFN-γ分泌和增殖，但它们对相同的TLTF诱导的反应没有影响。然而，TPK抑制剂染料木黄酮强烈抑制了TLTF诱导的两种类型反应细胞对IFN-γ分泌的激活以及TLTF诱导的小鼠CD8⁺CD4⁻MNC的增殖。离子霉素和十四酰佛波醇乙酸酯可以克服药物的抑制作用，这表明这些作用不是由于药物的非特异性细胞毒性。我们得出结论，TLTF通过PKC或PKA依赖性信号转导以外的途径激活CD8⁺T细胞，并且TPK可能参与了触发过程。
