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首页> 外文期刊>Infection and immunity >In vitro simulation of immunosuppression caused by Trypanosoma brucei: active involvement of gamma interferon and tumor necrosis factor in the pathway of suppression.
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In vitro simulation of immunosuppression caused by Trypanosoma brucei: active involvement of gamma interferon and tumor necrosis factor in the pathway of suppression.

机译：布鲁氏锥虫引起的免疫抑制的体外模拟：γ干扰素和肿瘤坏死因子积极参与抑制途径。

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Experimental infections of mice with the African trypanosome Trypanosoma brucei lead to a profound state of T-cell unresponsiveness in the lymph node cell (LNC) compartment. This suppression is mediated by macrophage-like cells which inhibit interleukin 2 (IL-2) secretion and down-regulate IL-2 receptor expression (M. Sileghem, A. Darji, R. Hamers, M. Van de Winkel, and P. De Baetselier, Eur. J. Immunol. 19:829-835, 1989). Similar suppressive cells can be generated in vitro by pulsing 2C11-12 macrophage hybridoma cells with opsonized T. brucei parasites (2C11-12P cells). Cocultures of 2C11-12P cells and LNCs secrete higher levels of gamma interferon (IFN-gamma), and the hyperproduction of IFN-gamma was found to be confined to CD8+ lymphoid cells. Elimination of CD8+ cells from cocultures of 2C11-12P cells and LNCs restores the T-cell proliferative response. Furthermore, addition of neutralizing anti-IFN-gamma antibodies to the cocultures reduces the level of suppression and concomitantly restores the level of IL-2 receptor expression. Hence, IFN-gamma plays a cardinal role in this in vitro model for T. brucei-elicited immunosuppression. Cocultures of LNCs and 2C11-12P cells in a two-chamber culture system further demonstrated that cell-cell contact is required for hyperproduction of IFN-gamma and, moreover, that IFN-gamma cooperates with a 2C11-12P-derived diffusible factor to exert its suppressive activity. Finally, tumor necrosis factor alpha (TNF-alpha produced by 2C11-12P cells was found to be implicated in the hyperproduction of IFN-gamma, since addition of neutralizing anti-TNF-alpha antibodies to cocultures reduced the level of suppression and concomitantly abrogated the hyperproduction of IFN-gamma. Collectively, our findings indicate that T. brucei-elicited suppressive 2C11-12 macrophage cells differentially influence T-cell subpopulations: (i) CD8+ cells are signaled via cell-cell contact to produce IFN-gamma, and TNF-alpha is implicated in this process, and (ii) locally produced IFN-gamma and macrophage-released factors act in concert to inhibit CD4+ and CD8+ T-cell proliferative responses.
机译：非洲锥虫Trypanosoma brucei对小鼠的实验性感染导致淋巴结细胞（LNC）隔室中的T细胞无反应状态达到深刻状态。这种抑制作用是由抑制白介素2（IL-2）分泌并下调IL-2受体表达的巨噬细胞样细胞介导的（M. Sileghem，A。Darji，R。Hamers，M。Van de Winkel和P. De Baetselier，Eur.J.Immunol.19：829-835，1989）。通过用调理过的布鲁氏杆菌寄生虫脉冲2C11-12巨噬细胞杂交瘤细胞（2C11-12P细胞），可以在体外产生类似的抑制性细胞。 2C11-12P细胞和LNC的共培养物分泌更高水平的γ干扰素（IFN-γ），并且发现IFN-γ的高产量仅限于CD8 +淋巴样细胞。从2C11-12P细胞和LNC的共培养物中消除CD8 +细胞可恢复T细胞增殖反应。此外，向共培养物中添加中和性抗IFN-γ抗体降低了抑制水平，并同时恢复了IL-2受体表达水平。因此，IFN-γ在布鲁氏杆菌引起的免疫抑制的体外模型中起着主要作用。 LNC和2C11-12P细胞在两腔培养系统中的共培养进一步证明，细胞-细胞接触是IFN-γ高产所必需的，此外，IFN-γ与2C11-12P衍生的扩散因子协同发挥作用它的抑制活性。最后，发现肿瘤坏死因子α（由2C11-12P细胞产生的TNF-α与IFN-γ的过量产生有关，因为在共培养物中添加中和性抗TNF-α抗体降低了抑制水平，并同时废除了抑制作用）。总的来说，我们的发现表明，布鲁氏杆菌引起的抑制性2C11-12巨噬细胞具有差异性地影响T细胞亚群：（i）CD8 +细胞通过细胞与细胞的接触发出信号，从而产生IFN-γ和TNF。 -α参与该过程，并且（ii）局部产生的IFN-γ和巨噬细胞释放的因子协同作用以抑制CD4 +和CD8 + T细胞增殖反应。

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