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Functional and phenotypic changes in human lymphocytes after coincubation with Leishmania donovani in vitro.

机译:在体外与利什曼原虫共孵育后人类淋巴细胞的功能和表型变化。

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In this paper we describe functional and phenotypic changes in T cells after in vitro coincubation of peripheral blood mononuclear cells (PBMC) and Leishmania donovani parasites at different parasite/peripheral blood mononuclear cell ratios. The phytohemagglutinin (PHA)-induced lymphoproliferative response was reduced by the coincubation, and at the maximal parasite/peripheral blood mononuclear cell ratio used (7.5:1), the average response was less than 40% of the response in the absence of parasites. The cause of the reduction in lymphoproliferation is not clear, but it requires live parasites. Interleukin-1 production was unaffected, the levels of soluble interleukin-2 receptor in supernatants were not changed by the coincubation, and the addition of exogenous interleukin-2 failed to revert the suppressive effect of the parasites. In addition to the reduction in lymphocyte proliferation, phenotypic lymphocyte changes were observed. Cell surface expression of the CD3 antigen, which is part of the CD3-T-cell receptor complex, was significantly reduced with increasing parasite/peripheral blood mononuclear cell ratios; the reduction was general in the sense that the parasites caused a shift in the fluorescent intensities of anti-CD3 labeled cells toward lower values, without affecting the distribution pattern. In contrast, the parasites altered the CD25 (interleukin-2 receptor) expression on PHA-stimulated cells from a homogenous CD25-positive population to two populations, one small and without CD25 expression and the other, larger population with only a slight reduction in size and CD25 expression. In addition to the changes in expression of surface antigens, a general reduction in the size of PHA-stimulated lymphocytes after coincubation with the parasites was observed. The data presented thus suggest that the inhibition of the proliferative response to PHA by live L. donovani in vitro is associated with early processes in lymphocyte activation. Further studies on the inhibitory phenomena described may be of potential significance in the investigation of the suppressive mechanisms in human visceral leishmaniasis.
机译:在本文中,我们描述了外周血单核细胞(PBMC)和利什曼原虫多虫寄生虫在不同寄生虫/外周血单核细胞比率的体外共孵育后T细胞的功能和表型变化。共孵育降低了植物血凝素(PHA)诱导的淋巴增生反应,在使用最大的寄生虫/外周血单核细胞比例(7.5:1)时,平均应答小于没有寄生虫时应答的40%。淋巴细胞增殖减少的原因尚不清楚,但需要活的寄生虫。共孵育不会影响白细胞介素-1的产生,上清液中可溶性白细胞介素-2受体的水平没有改变,并且添加外源白细胞介素-2不能恢复寄生虫的抑制作用。除了减少淋巴细胞增殖,还观察到表型淋巴细胞的变化。 CD3抗原是CD3-T细胞受体复合物的一部分,其细胞表面表达随寄生虫/外周血单核细胞比例的增加而显着降低。这种降低是一般性的,因为寄生虫会导致抗CD3标记的细胞的荧光强度向较低值移动,而不影响分布模式。相比之下,这些寄生虫将PHA刺激的细胞上CD25(白介素2受体)的表达从同质CD25阳性群体改变为两个群体,一个很小,没有CD25表达,另一个更大,只有很小的体积减小和CD25表达。除了表面抗原表达的变化外,与寄生虫共孵育后,观察到PHA刺激的淋巴细胞大小也普遍减少。因此,所提供的数据表明活的体外诺氏乳酸杆菌对PHA增殖反应的抑制与淋巴细胞活化的早期过程有关。所述抑制现象的进一步研究可能在研究人类内脏利什曼病的抑制机制中具有潜在的意义。

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