CD28-deficient mice generate an impaired Th2 response to Schistosoma mansoni infection
CD28-deficient mice generate an impaired Th2 response to Schistosoma mansoni infection
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DOI：
10.1002/eji.1830261027
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发表时间：
1996-10-01
影响因子：
5.4
通讯作者：
Lee, KP
中科院分区：
文献类型：
--
作者：
King, CL;Jia, XL;Lee, KP
CD28与T细胞的结合为T细胞的激活和分化提供了必要的共刺激信号。最近的研究结果表明，T辅助（Th）2细胞的启动比Th1细胞更依赖于CD28的激活。本研究探讨了由于基因靶向而缺乏CD28表达的小鼠是否能够在感染血管内吸虫寄生虫曼氏血吸虫时产生Th2反应特征。突变小鼠和对照小鼠要么在足垫中接种mansoni S.卵（Th2反应的有效诱导剂），要么经皮感染寄生虫。分别在第12天和第8周收集引流淋巴结（脚垫注射后）或脾脏细胞（自然感染后），检测细胞因子对鸡蛋抗原的反应。cd28缺陷小鼠（-/-）产生的卵细胞抗原驱动的白细胞介素(IL)-4和IL-5的产生减少（分别为cd28表达（+/+）的幼崽的5- 17倍）。相比之下，突变小鼠和对照小鼠的淋巴细胞增殖和卵细胞抗原产生的干扰素(IFN) γ是相同的。感染的CD28-/-小鼠的免疫球蛋白分泌也减少。与CD28+/+小鼠相比，CD28-/-小鼠血清中寄生虫抗原特异性IgG1和多克隆IgE水平显著降低，缺乏CD28表达对困在肝脏中的卵周围肉芽肿的形成没有影响，但增加了小鼠对原发性血吸虫病感染的易感性。这些研究表明，CD28激活有助于T细胞启动，从而产生对血管内居住的寄生虫的Th2反应。
Engagement of CD28 on T cells provides a co-stimulatory signal necessary for T cell activation and differentiation. Recent findings suggest that priming of T helper (Th)2 cells is more dependent on CD28 activation than Th1 cells. The present study examines whether mice that lack expression of CD28 as a result of gene targeting are capable of generating a Th2 response characteristic during infection with the intravascular trematode parasite Schistosoma mansoni. Mutant and control mice were either inoculated in the footpad with S. mansoni eggs (a potent inducer of a Th2 response) or infected percutaneously with the parasite. Draining lymph nodes (after footpad injection) or spleen cells (after natural infection) were harvested at 12 days and 8 weeks, respectively and examined for cytokine responses to egg antigens. CD28-deficient mice (-/-) generated diminished egg antigen-driven interleukin (IL)-4 and IL-5 production (by 5- to 17-fold, respectively) compared to CD28-expressing (+/+) littermates. In contrast, lymphocyte proliferation and interferon (IFN)-gamma production to egg antigens were equivalent for mutant and control mice. Infected CD28-/- mice also had reduced immunoglobulin secretion. Serum levels of parasite antigen-specific IgG1 and polyclonal IgE were significantly diminished in CD28-/- compared to CD28+/+ mice, Lack of CD28 expression had no effect on granuloma formation around eggs trapped in the Liver, but increased susceptibility of mice to primary schistosomiasis infection, These studies indicate that CD28 activation contributes to T cell priming required for generation of a Th2 response to an intravascular dwelling helminth parasite.