Gut intraepithelial lymphocytes induce immunity against Cryptosporidium infection through a mechanism involving gamma interferon production
Gut intraepithelial lymphocytes induce immunity against Cryptosporidium infection through a mechanism involving gamma interferon production
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DOI：
10.1128/iai.65.8.3074-3079.1997
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发表时间：
1997-08-01
影响因子：
3.1
通讯作者：
McDonald, V
中科院分区：
文献类型：
--
作者：
Culshaw, RJ;Bancroft, GJ;McDonald, V
小鼠隐孢子虫感染的免疫控制依赖于CD 4（+）T细胞和γ干扰素（IFN-γ）的产生，但迄今为止，感染局部产生IFN-γ的粘膜T细胞尚未被表征。我们以前的研究表明，抗胃寄生虫鼠隐孢子虫的免疫力可以通过来自先前感染免疫活性小鼠的小肠上皮内淋巴细胞（IEL）过继转移到成年SCID（严重联合免疫缺陷）小鼠，但前提是供体CD 4（+）T细胞是完整的。本研究检测了IFN-γ在SCID小鼠免疫IEL介导的效应机制中是否重要。在给予免疫IEL的SCID小鼠中，通过用仓鼠抗小鼠IFN-γ-中和单克隆抗体治疗来防止对小鼠衣原体感染的抗性的发展，但是在停止抗体治疗后，小鼠从感染中恢复。在进一步的实验中，使用酶联免疫斑点（ELISPOT）技术来比较来自C.小鼠免疫和未处理供体小鼠。用伴刀豆球蛋白A或大鼠抗小鼠CD 3单克隆抗体刺激后，检测到免疫产生IFN-γ的细胞数量多于幼稚IEL群体。来自小鼠免疫小鼠的少量IEL，但不是来自幼稚小鼠的IEL，当与可溶性卵囊抗原一起培养时，也会产生IFN-γ，但这只有在γ射线照射的脾细胞与免疫IEL共培养时才会发生，这些结果表明，IEL在产生对隐孢子虫的免疫中是重要的，并且它们的关键功能之一是在感染部位产生IFN-γ。
Immunological control of infection with cryptosporidia in mice is dependent on CD4(+) T cells and the production of gamma interferon (IFN-gamma), but to date, the mucosal T cells which produce IFN-gamma local to the infection have not been characterized. We previously showed that immunity against the gastric parasite Cryptosporidium muris could be adoptively transferred to adult SCID (severe combined immunodeficiency) mice with small intestinal intraepithelial lymphocytes (IEL) from previously infected immunocompetent mice, but only if the donor CD4(+) T cells were intact, The present investigation examined whether IFN-gamma was important in the effector mechanisms mediated by immune IEL in SCID mice. The development of resistance against C, muris infection in SCID mice given immune IEL was prevented by treatment with a hamster anti-mouse IFN-gamma-neutralizing monoclonal antibody, but following cessation of antibody treatment, the mice recovered from infection, In further experiments, an enzyme-linked immunospot (ELISPOT) technique was used to compare frequencies of IFN-gamma-producing cells in activated T-cell populations from C. muris-immune and naive donor mice. Stimulation with concanavalin A or a rat anti-mouse CD3 monoclonal antibody resulted in detection of greater numbers of cells producing IFN-gamma from immune than naive IEL populations, Small numbers of IEL from C, muris-immune mice, but not from naive mice, also produced IFN-gamma when cultured with soluble oocyst antigen, but this occurred only if gamma-irradiated spleen cells were cocultured with the immune IEL, These results suggested that IEL,were important in the generation of immunity to Cryptosporidium and that one of their crucial functions was to produce IFN-gamma at the site of infection.