Deficient humoral responses underlie susceptibility to Toxoplasma gondii in CD4-deficient mice
Deficient humoral responses underlie susceptibility to Toxoplasma gondii in CD4-deficient mice
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DOI：
10.1128/iai.70.1.185-191.2002
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发表时间：
2002-01-01
影响因子：
3.1
通讯作者：
Sayles, PC
中科院分区：
文献类型：
--
作者：
Johnson, LL;Sayles, PC
在缺乏 CD4 表达的小鼠中研究了对弓形虫感染的抵抗力。经口感染 ME49 囊肿后，与野生型对照小鼠相比，这些小鼠产生了更多的脑囊肿，并且存活时间更短。在用弓形虫 ts-4 菌株免疫后，CD4 缺陷小鼠表现出对强毒 RH 速殖子攻击感染的抵抗力受损。因此，CD4表达缺陷会增加小鼠对原发性经口弓形虫包囊感染的易感性，并损害其成功接种疫苗的能力。来自弓形虫感染、CD4 缺陷小鼠的血液或脾脏的 CD8(+) T 细胞表达激活标记的频率与受感染的野生型小鼠相似。体外 IFN-γ 的产生适度降低，血清中弓形虫特异性免疫球蛋白 G2a 的水平显着低于野生型小鼠。对接种 ts-4 的 CD4 缺陷小鼠施用弓形虫免疫血清可显着提高其对 RE 攻击的抵抗力。此外，通过给予免疫血清，慢性感染 ME49 的 CD4 缺陷小鼠的存活率显着延长。这些结果表明，除了已知对耐药性至关重要的CD8(+) T细胞和IFN-γ之外，CD4(+)细胞还通过其作为产生同种型转换抗体的辅助细胞的作用，对免疫小鼠免受慢性弓形虫感染和高毒力速殖子的攻击感染做出了显着贡献。
Resistance to infection with Toxoplasma gondii was studied in mice lacking CD4 expression. Such mice developed more brain cysts and survived for a shorter time than did wild-type controls after peroral infection with ME49 cysts. After immunization with the ts-4 strain of T. gondii, CD4-deficient mice exhibited impaired resistance to a challenge infection with virulent RH tachyzoites. Thus, deficient CD4 expression increases the susceptibility of mice to a primary peroral T. gondii infection with cysts and impairs their ability to be successfully vaccinated. CD8(+) T cells from blood or spleens of Toxoplasma-infected, CD4-deficient mice expressed markers of activation at frequencies similar to those of infected wild-type mice. Production of IFN-gamma in vitro was moderately depressed, and levels of Toxoplasma-specific immunoglobulin G2a in serum were substantially lower than in wild-type mice. Administration of Toxoplasma-immune serum to ts-4-vaccinated CD4-deficient mice significantly improved their resistance to RE challenge. Also, the survival of CD4-deficient mice chronically infected with ME49 was significantly prolonged by administration of immune serum. These results demonstrate that in addition to CD8(+) T cells and IFN-gamma, which are known to be critical for resistance, CD4(+) cells also contribute significantly to protection against chronic T. gondii infections and against challenge infections with highly virulent tachyzoites in immunized mice via their role as helper cells for production of isotype-switched antibodies.