Yamashita T, Boros D L
Department of Immunology and Microbiology, Wayne State University School of Medicine, Detroit, MI 48201.
J Immunol. 1990 Jul 15;145(2):724-31.
In murine schistosomiasis mansoni the soluble egg Ag (SEA)-induced L3T4+ T cell-mediated circumoval granulomatous response peaks at the acute stage (8w) and undergoes Lyt-1+, Lyt-2+ suppressor cell mediated down-modulation at the chronic stage (20w) of the infection. In the present study lymphoproliferation, IL-2 production, utilization, and IL-2R display were examined in splenic lymphocytes of infected mice. The L3T4+ subset was the major SEA-specific proliferative population at both stages of the infection. Chronic infection spleen cells or the L3T4+ subset proliferated less compared with their acute infection counterparts. Elimination of the Lyt-2+ subset did not improve diminished proliferation. Chronic infection cells and the Lyt-2+ subset stimulated with SEA and exogenous rIL-2 regained their proliferative ability to a level comparable with acute infection cells. Ag-stimulated acute infection T cells produced 40 to 50 chronic infection cells less than 5 U/ml IL-2. Elimination of L3T4+ T cells diminished, and the Lyt-2+ T cells left unchanged IL-2 production in the acute infection cells. Elimination of Lyt-2+ subset from the chronic infection population did not enhance IL-2 production. Exogenously added rIL-2 was equally utilized by acute or chronic infection T cells. Scatchard plots of [125I]IL-2 binding showed similar numbers of high affinity receptors on acute (189) and chronic infection cells (118), but the number of low affinity receptors was higher on the acute (2229) vs the chronic infection lymphocytes (578). Analysis of IL-2R expression by two-color fluorescence and flow cytometry revealed that 30 to 40% of the acute, chronic infection L3T4+ cells displayed receptor. Receptor expression increased by added SEA, or SEA + rIL-2. R display among Lyt-2+ cells was only 12 to 18%. SEA stimulation enhanced receptor display more among the acute, SEA + rIL-2 stimuli raised receptor expression only among chronic infection lymphocytes. These data do not show inherent defect in IL-2R display, or utilization in chronic infection T cells. Diminished IL-2 production appears to be the cause of decreased T cell responsiveness.
在小鼠曼氏血吸虫病中，可溶性虫卵抗原（SEA）诱导的L3T4 + T细胞介导的虫卵周围肉芽肿反应在急性期（8周）达到峰值，并在感染的慢性期（20周）受到Lyt-1 +、Lyt-2 +抑制细胞介导的下调。在本研究中，检测了感染小鼠脾淋巴细胞中的淋巴细胞增殖、IL-2产生、利用情况以及IL-2R表达。L3T4 +亚群是感染两个阶段中主要的SEA特异性增殖群体。与急性感染的对应细胞相比，慢性感染脾细胞或L3T4 +亚群的增殖较少。去除Lyt-2 +亚群并不能改善增殖减少的情况。用SEA和外源性rIL-2刺激慢性感染细胞和Lyt-2 +亚群，其增殖能力恢复到与急性感染细胞相当的水平。抗原刺激的急性感染T细胞产生的IL-2比慢性感染细胞少40至50，小于5 U/ml。去除L3T4 + T细胞会减少急性感染细胞中的IL-2产生，而Lyt-2 + T细胞则无变化。从慢性感染群体中去除Lyt-2 +亚群并不能增强IL-2的产生。外源性添加的rIL-2被急性或慢性感染T细胞同等利用。[125I]IL-2结合的Scatchard图显示，急性感染细胞（189个）和慢性感染细胞（118个）上高亲和力受体的数量相似，但急性感染淋巴细胞（2229个）上低亲和力受体的数量高于慢性感染淋巴细胞（578个）。通过双色荧光和流式细胞术分析IL-2R表达，发现30%至40%的急性、慢性感染L3T4 +细胞表达受体。添加SEA或SEA + rIL-2后，受体表达增加。Lyt-2 +细胞中的受体表达仅为12%至18%。SEA刺激在急性感染细胞中增强受体表达的作用更明显，SEA + rIL-2刺激仅在慢性感染淋巴细胞中提高受体表达。这些数据并未显示慢性感染T细胞中IL-2R表达或利用存在内在缺陷。IL-2产生减少似乎是T细胞反应性降低的原因。
