Kierszenbaum F, Moretti E, Sztein M B
Department of Microbiology and Public Health, Michigan State University, East Lansing 48824.
Immunology. 1991 Oct;74(2):317-22.
Trypanosoma cruzi, the causative agent of Chagas' disease, suppresses immune responses during the acute phase and has been shown to induce multiple cellular alterations in activated human T lymphocytes. However, no information is available regarding the effects of this parasite on human B cells. Using an in vitro culture system, in which purified T. cruzi are co-cultured with either peripheral blood mononuclear cells (PBMC) or B-cell-enriched preparations (BCE), we studied whether the organism can induce alterations in DNA synthesis after stimulation with Pansorbin (PS). This response was markedly reduced by the parasite at both suboptimal and optimal PS concentrations, and the extent of the inhibition was augmented as the parasite concentration was increased. Maximal reduction in DNA synthesis was observed when the trypanosomes were incorporated into the cultures at 0 time (i.e. together with PS); the effect was of a much lesser magnitude and undetectable when the parasites were added at 24 and 48 hr, respectively. These results imply that T. cruzi affects a relatively early event during B-cell stimulation. This inference was confirmed by the finding that the proportion of PS-stimulated B cells expressing interleukin-2 (IL-2) receptors was significantly reduced when the parasite was present in the culture. Addition of recombinant human IL-2 did not restore B-cell responsiveness to normal levels. Suppressed B-cell responses were also observed when T. cruzi was separated from the PBMC or the BCE by a cell-impermeable filter, indicating that a soluble factor(s) released by the organism mediated the effect. Accordingly, supernatants of T. cruzi suspensions were found to be suppressive. These results demonstrate for the first time that T. cruzi can affect human B-cell responses and that the mechanism involves inhibition of IL-2 receptor expression.
克氏锥虫是恰加斯病的病原体，在急性期会抑制免疫反应，并且已被证明能在活化的人类T淋巴细胞中诱导多种细胞改变。然而，关于这种寄生虫对人类B细胞的影响尚无相关信息。我们使用一种体外培养系统，将纯化的克氏锥虫与外周血单核细胞（PBMC）或富含B细胞的制剂（BCE）共同培养，研究该生物体在受到泛福舒（PS）刺激后是否能诱导DNA合成的改变。在次优和最优PS浓度下，寄生虫均显著降低了这种反应，并且随着寄生虫浓度的增加，抑制程度增强。当锥虫在0时刻（即与PS一起）加入培养物时，观察到DNA合成的最大减少；当寄生虫分别在24小时和48小时加入时，这种效应的程度要小得多且无法检测到。这些结果表明，克氏锥虫影响B细胞刺激过程中相对较早的事件。这一推断得到了以下发现的证实：当培养物中存在寄生虫时，表达白细胞介素-2（IL-2）受体的PS刺激的B细胞比例显著降低。添加重组人IL-2并未将B细胞反应性恢复到正常水平。当克氏锥虫通过细胞不可渗透的滤器与PBMC或BCE分离时，也观察到B细胞反应受到抑制，这表明该生物体释放的一种或多种可溶性因子介导了这种效应。因此，发现克氏锥虫悬浮液的上清液具有抑制作用。这些结果首次证明，克氏锥虫可影响人类B细胞反应，其机制涉及抑制IL-2受体表达。
