Sztein M B, Kierszenbaum F
Department of Pediatrics, University of Maryland School of Medicine, Baltimore 21201.
Immunology. 1991 Jun;73(2):180-5.
African sleeping sickness is accompanied by a severe immunosuppression. As part of our efforts to examine the mechanisms by which this suppressive state is induced, we studied alterations in human T-lymphocyte function caused by Trypanosoma brucei rhodesiense. To this end, we used an in vitro system in which phytohaemagglutinin (PHA)-stimulated human peripheral blood mononuclear cells (PBMC) were cultured in a medium containing soluble, non-dialysable parasite products. We were able to demonstrate significant suppression of both lympho-proliferation and interleukin-2 receptor (IL-2R) expression. These effects were found to be dose-dependent and reversible after 48 hr of culture. The suppressive effects of living trypanosomes and the soluble parasite products on lympho-proliferation and interleukin-2 receptor expression were similar in that both precluded the entry of PHA-activated PBMC into the cell cycle. Eighty to ninety-eight per cent of the activated cells remained arrested in the G0/G1a (early G1) phase even 48 hr after stimulation, i.e. when last tested. Parasite-induced expression could not be overcome by the addition of recombinant human IL-2. These results suggest that immunosuppression associated with African trypanosomiasis may result from parasite-induced alteration of very early events during lymphocyte activation, leading to a virtually complete block in cell cycle progression and inhibition of IL-2R expression.
非洲昏睡病伴有严重的免疫抑制。作为我们探究这种抑制状态诱发机制的努力的一部分，我们研究了布氏罗得西亚锥虫引起的人类T淋巴细胞功能的改变。为此，我们使用了一种体外系统，其中用植物血凝素（PHA）刺激的人类外周血单核细胞（PBMC）在含有可溶性、不可透析的寄生虫产物的培养基中培养。我们能够证明淋巴细胞增殖和白细胞介素-2受体（IL-2R）表达均受到显著抑制。这些作用呈剂量依赖性，且在培养48小时后是可逆的。活锥虫和可溶性寄生虫产物对淋巴细胞增殖和白细胞介素-2受体表达的抑制作用相似，因为两者都阻止了PHA激活的PBMC进入细胞周期。即使在刺激后48小时（即最后一次检测时），80%至98%的活化细胞仍停滞在G0/G1a（早期G1）期。添加重组人IL-2无法克服寄生虫诱导的表达。这些结果表明，与非洲锥虫病相关的免疫抑制可能是由于寄生虫诱导淋巴细胞激活过程中非常早期事件的改变，导致细胞周期进程几乎完全受阻和IL-2R表达受到抑制。
