Mice from a genetically resistant background lacking the interferon gamma receptor are susceptible to infection with Leishmania major but mount a polarized T helper cell 1-type CD4+ T cell response.
Mice from a genetically resistant background lacking the interferon gamma receptor are susceptible to infection with Leishmania major but mount a polarized T helper cell 1-type CD4+ T cell response.
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DOI：
10.1084/jem.181.3.961
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发表时间：
1995-03-01
期刊：
影响因子：
--
通讯作者：
Louis JA
中科院分区：
文献类型：
--
作者：
Swihart K;Fruth U;Messmer N;Hug K;Behin R;Huang S;Del Giudice G;Aguet M;Louis JA
干扰素(IFN) γ受体配体结合链编码基因同源破坏的小鼠，来源于一种对利什曼原虫感染具有遗传抗性的菌株，已被用于进一步研究该细胞因子在体内功能CD4+ T细胞亚群分化和感染抗性中的作用。野生型129/Sv/Ev小鼠对这种寄生虫的感染具有抵抗力，仅产生小病变，并在6周内自行消退。相反，缺乏IFN- γ受体的小鼠出现较大的进展性病变。感染后，野生型和基因敲除小鼠的淋巴结（LN）和脾脏显示产生ifn - γ的CD4+细胞扩增，这是通过测量特异性刺激的CD4+ T细胞上清液中的ifn - γ，通过枚举产生ifn - γ的T细胞，以及通过ifn - γ转录物的Northern blot分析显示的。在感染野生型或缺陷型小鼠体外刺激LN或脾脏细胞的上清液中未检测到具有生物活性的白细胞介素（IL） 4。用IL-4特异性引物进行逆转录聚合酶链反应分析显示，两种小鼠LN中IL-4信息水平相似。观察到的IL-4信息水平与类似感染的C57BL/6小鼠相当，显著低于BALB/c小鼠的水平。抗干扰素γ治疗两种类型的小鼠未能改变感染后产生的细胞因子的模式。这些数据表明，即使在缺乏ifn - γ受体的情况下，T辅助细胞（Th） 1型反应仍然在遗传抗性小鼠中发展，没有Th2细胞扩增的证据。
Mice with homologous disruption of the gene coding for the ligand- binding chain of the interferon (IFN) gamma receptor and derived from a strain genetically resistant to infection with Leishmania major have been used to study further the role of this cytokine in the differentiation of functional CD4+ T cell subsets in vivo and resistance to infection. Wild-type 129/Sv/Ev mice are resistant to infection with this parasite, developing only small lesions, which resolve spontaneously within 6 wk. In contrast, mice lacking the IFN- gamma receptor develop large, progressing lesions. After infection, lymph nodes (LN) and spleens from both wild-type and knockout mice showed an expansion of CD4+ cells producing IFN-gamma as revealed by measuring IFN-gamma in supernatants of specifically stimulated CD4+ T cells, by enumerating IFN-gamma-producing T cells, and by Northern blot analysis of IFN-gamma transcripts. No biologically active interleukin (IL) 4 was detected in supernatants of in vitro-stimulated LN or spleen cells from infected wild-type or deficient mice. Reverse transcription polymerase chain reaction analysis with primers specific for IL-4 showed similar IL-4 message levels in LN from both types of mice. The IL-4 message levels observed were comparable to those found in similarly infected C57BL/6 mice and significantly lower than the levels found in BALB/c mice. Anti-IFN-gamma treatment of both types of mice failed to alter the pattern of cytokines produced after infection. These data show that even in the absence of IFN-gamma receptors, T helper cell (Th) 1-type responses still develop in genetically resistant mice with no evidence for the expansion of Th2 cells.