Murine schistosomiasis mansoni: coordinate cytokine regulation and differences in cellular immune responses of granuloma cells and splenocytes to endogenous and exogenous schistosome egg antigens
Murine schistosomiasis mansoni: coordinate cytokine regulation and differences in cellular immune responses of granuloma cells and splenocytes to endogenous and exogenous schistosome egg antigens
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DOI：
10.1046/j.1365-3024.2001.00420.x
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发表时间：
2001-11-01
影响因子：
2.2
通讯作者：
Stavitsky, AB
中科院分区：
文献类型：
--
作者：
King, CL;Jia, XL;Stavitsky, AB
为了更好地了解调节血吸虫肉芽肿性炎症的细胞免疫机制。Mansoni ova感染后6-19周，我们检测了内源性和外源性血吸虫卵抗原(SEA)对肉芽肿细胞和脾细胞淋巴细胞增殖和细胞因子表达的动态影响。与脾细胞相比，位于抗原释放部位的肉芽肿细胞(部分CD4(+)细胞)被内源性SEA高度激活并最终分化，表现为体外白介素4(IL)-4、IL-5和干扰素(干扰素)-γ分泌细胞的频率增加了10倍以上，构成细胞因子的产生水平更高，无法向内源性或外源性SEA增殖。肉芽肿细胞产生的内源性细胞因子是协同调节的，外源性SEA对内源性细胞因子的促进作用很小，并且与肉芽肿性炎症有时间相关性。而外源性SEA则较强地诱导IL-4、IL-5、IL-10和干扰素-γ的产生以及淋巴细胞的增殖，与肉芽肿性炎症的动态变化关系不大。这些结果表明，细胞因子对内源性SEA的反应与肉芽肿性炎症的相关性比对外源性SEA的反应更好。此外，肉芽肿细胞和脾细胞表现出明显不同的增殖反应和细胞因子的表达动态，提示SEA反应性淋巴细胞如何在淋巴组织和肉芽肿之间运输对于更好地理解肉芽肿炎症及其调控机制至关重要。
To better understand the cellular immune mechanisms that regulate granulomatous inflammation to Schistosoma. mansoni ova, we examined the dynamics of lymphocyte proliferation and cytokine expression by granuloma cells and splenocytes to endogenous and exogenous schistosome egg antigen (SEA) 6-19 weeks postinfection. Compared to splenocytes, granuloma cells (partially CD4(+) cells) which are at the site of antigen release were highly activated by endogenous SEA and terminally differentiated as indicated by the more than 10-fold greater frequency of ex vivo interleukin (IL)-4, IL-5 and interferon (IFN)-gamma -secreting cells, greater levels of constitutive cytokine production and failure to proliferate to either endogenous or exogenous SEA. Endogenous cytokine production by granuloma cells was coordinately regulated, enhanced little by exogenous SEA, and temporally correlated with granulomatous inflammation. By contrast, CD4(+) splenocytes produced comparatively little cytokine release by endogenous antigen, whereas exogenous SEA strongly induced IL-4, IL-5, IL-10 and IFN-gamma production and lymphocyte proliferation that correlated poorly with the dynamics of granulomatous inflammation. These results show that cytokine responses to endogenous SEA correlated better with granulomatous inflammation than responses to exogenous SEA. Furthermore, granuloma cells and splenocytes demonstrated strikingly different proliferative responses and dynamics of cytokine expression, suggesting that how SEA reactive lymphocytes traffic between lymphoid tissues and the granuloma is critical to a better understanding of the mechanisms of granulomatous inflammation and its modulation.