Wilson M E, Sandor M, Blum A M, Young B M, Metwali A, Elliott D, Lynch R G, Weinstock J V
Department of Internal Medicine, University of Iowa, Iowa City 52242, USA.
J Immunol. 1996 Mar 15;156(6):2231-9.
BALB/c mice are susceptible to infection with the visceralizing species of Leishmania, Leishmania chagasi. The parasite load initially rises in the liver and spontaneously subsides, whereas parasite multiplication begins later and remains lower in the spleen. To investigate whether this organ-specific multiplication of L. chagasi correlates with localized immune responses, we compared cytokine production by splenic vs hepatic immune cells. Livers from infected mice contained granulomas harboring intracellular L. chagasi amastigotes, whereas few amastigotes were present in the spleen. FACS analysis granuloma cells showed granuloma lymphocytes expressed a memory/effector phenotype. Granuloma cells cultured in vitro produced IL-10 and IL-6 but no detectable IFN-gamma, IL-4 or IL-5. In contrast, splenocytes from the same animals secreted IFN-gamma, IL-4, IL-6, and IL-10. T cells were depleted from granuloma cells by immune lysis, and the results indicated that IL-10 and IL-6 were derived at least in part from a non-T cell compartment. Paradoxically, FACS-purified Thy-1+ granuloma lymphocytes were able to produce IFN-gamma in the absence of other granuloma cells, suggesting IFN-gamma production might usually be inhibited by a granuloma-associated non-T cell element. Coculture of splenocytes with either granuloma cells or supernatants from granuloma cultures inhibited the usual splenocyte production of IFN-gamma and IL-4 but not IL-10. Thus, there may be a unique granuloma-associated suppressive factor accounting for the absence of IFN-gamma in hepatic granuloma cultures. It may be the absence of IFN-gamma in the liver and presence in the spleen that allows or inhibits parasite survival, respectively, in these different locations.
BALB/c小鼠易受内脏利什曼原虫（Leishmania chagasi）感染。寄生虫负荷最初在肝脏中升高，随后自发下降，而寄生虫增殖在脾脏中开始较晚且水平较低。为了研究恰加斯利什曼原虫的这种器官特异性增殖是否与局部免疫反应相关，我们比较了脾免疫细胞与肝免疫细胞产生细胞因子的情况。感染小鼠的肝脏中含有肉芽肿，其中有细胞内恰加斯利什曼原虫无鞭毛体，而脾脏中几乎没有无鞭毛体。对肉芽肿细胞进行的流式细胞术分析显示，肉芽肿淋巴细胞表达记忆/效应细胞表型。体外培养的肉芽肿细胞产生白细胞介素-10（IL-10）和白细胞介素-6（IL-6），但未检测到干扰素-γ（IFN-γ）、白细胞介素-4（IL-4）或白细胞介素-5（IL-5）。相比之下，同一动物的脾细胞分泌IFN-γ、IL-4、IL-6和IL-10。通过免疫裂解从肉芽肿细胞中去除T细胞，结果表明IL-10和IL-6至少部分来源于非T细胞区室。矛盾的是，通过流式细胞术纯化的Thy-1 +肉芽肿淋巴细胞在没有其他肉芽肿细胞的情况下能够产生IFN-γ，这表明IFN-γ的产生通常可能受到与肉芽肿相关的非T细胞成分的抑制。脾细胞与肉芽肿细胞或肉芽肿培养上清液共培养可抑制脾细胞通常产生的IFN-γ和IL-4，但不抑制IL-10。因此，可能存在一种独特的与肉芽肿相关的抑制因子，导致肝肉芽肿培养物中缺乏IFN-γ。可能正是肝脏中缺乏IFN-γ而脾脏中存在IFN-γ，分别使得寄生虫在这些不同部位得以存活或受到抑制。
