IMPAIRMENT OF THE CELLULAR IMMUNE-RESPONSE IN ACUTE MURINE TOXOPLASMOSIS - REGULATION OF INTERLEUKIN-2 PRODUCTION AND MACROPHAGE-MEDIATED INHIBITORY EFFECTS
IMPAIRMENT OF THE CELLULAR IMMUNE-RESPONSE IN ACUTE MURINE TOXOPLASMOSIS - REGULATION OF INTERLEUKIN-2 PRODUCTION AND MACROPHAGE-MEDIATED INHIBITORY EFFECTS
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DOI：
10.1128/iai.62.7.2908-2916.1994
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发表时间：
1994-07-01
影响因子：
3.1
通讯作者：
KASPER, L
中科院分区：
文献类型：
--
作者：
HAQUE, S;KHAN, I;KASPER, L
在小鼠和人中均报告了对弓形虫的细胞免疫应答的抑制。本研究旨在探讨实验性小鼠弓形虫病过程中白细胞介素2（IL-2）产生下调的动力学和机制。对于这些调查，野生型（PTg）的细胞介导的免疫应答进行了比较，毒性较低的突变体寄生虫（PTgB），这是缺乏主要的表面抗原，p30（SAG-I）。感染A/J小鼠的脾细胞在感染的第一周内未能对弓形虫抗原作出反应而增殖。PTg和PTgB感染的A/J小鼠表现出显着减少刀豆球蛋白A（Con A）诱导的淋巴细胞增殖反应。此外，与感染PTgB的小鼠相比，感染野生型寄生虫的小鼠脾细胞的反应显著减弱。ConA的淋巴增殖反应在第7天达到最低点，并在感染后至少14天保持低于对照水平。到感染后第21天，对Con A和弓形虫抗原的反应恢复到第7天前观察到的水平。感染后第7天，小鼠脾细胞经ConA刺激后培养上清中IL-2含量显著低于正常小鼠。Scatchard分析表明，感染和正常小鼠脾细胞之间高亲和力IL-2受体的结合位点数或能力无显著差异。不同浓度的外源性IL-2均不能恢复感染小鼠淋巴细胞对ConA的增殖反应。7天感染小鼠的粘附巨噬细胞能够抑制ConA刺激后正常脾细胞产生IL-2。由感染细胞介导的抑制活性被逆转的抗体IL-10，但不转化生长因子P。有感染和正常脾细胞中的一氧化氮产生的水平微不足道。这些结果表明，在急性鼠弓形虫病，有一个明确的时期（第7天），在此期间，T细胞有丝分裂原和寄生虫抗原相关的淋巴细胞增殖反应减少。此外，IL-2的产生减少，IL-10的增加，这似乎介导，在一定程度上，所观察到的下调免疫力的弓形虫。
Depression of the cellular immune response to Toxoplasma gondii has been reported in both mice and humans. The present study was undertaken to determine the kinetics and mechanism of the observed downregulation of interleukin 2 (IL-2) production during experimental murine toxoplasmosis. For these investigations, the cell-mediated immune response to the wild type (PTg) was compared with that to the less-virulent mutant parasite (PTgB), which is deficient in the major surface antigen, p30 (SAG-I). Spleen cells from infected A/J mice failed to proliferate in response to Toxoplasma antigens during the first week of infection. Both PTg- and PTgB-infected A/J mice exhibited a significant reduction in the concanavalin A (Con A)-induced lymphoproliferative response. Further, the response of splenocytes from mice infected with the wild-type parasite was significantly diminished compared with that of mice infected with PTgB. The lymphoproliferative response to Con A reached its nadir at day 7 and remained below control levels for at least 14 days postinfection. By day 21 postinfection, the response to Con A and to Toxoplasma antigens was restored to the level observed prior to day 7. Con A-stimulated culture supernatants of spleen cells from mice on day 7 postinfection contained significantly less IL-2 than normal mice. There was no significant difference in the numbers of binding sites or capacity of high-affinity IL-2 receptors between infected and normal mouse splenocytes as determined by Scatchard analysis. Exogenous IL-2 at different concentrations failed to restore the proliferative response of lymphocytes from infected mice to Con A. Adherent macrophages from 7-day-infected mice were able to suppress IL-2 production by normal splenocytes following stimulation with Con A. The inhibitory activity mediated by infected cells was reversed by the antibody to IL-10 but not transforming growth factor P. There were insignificant levels of nitric oxide production in both infected and normal splenocytes. These results indicate that during acute murine toxoplasmosis, there is a well-defined period (day 7) during which both the T-cell mitogen and parasite antigen-associated lymphoproliferative response are reduced. Further, there is a reduction in the production of IL-2 and an increase in IL-10, which appear to mediate, in part, the observed downregulation of immunity to T.gondii.