Aguirre S A, Perryman L E, Davis W C, McGuire T C
Department of Veterinary Microbiology and Pathology, Washington State University, Pullman 99164, USA.
J Immunol. 1998 Aug 15;161(4):1891-900.
Resistance of adult C57BL/6 mice to severe Cryptosporidium parvum infection is dependent on CD4+alpha beta+ TCR lymphocytes. In this study, we demonstrated that treatment with anti-IFN-gamma mAb extended oocyst excretion 18 days longer, and anti-IL-4 mAb extended oocyst excretion at least 11 days longer than isotype control mAb treatment. Analysis of the specific activity of anti-IFN-gamma mAb present in treated mouse sera suggested that IFN-gamma may have a limited role in the resolution phase of infection. Changes were also documented in numbers of CD4+alpha beta+IFN-gamma+ and CD4+alpha beta+IL-4+ lymphocytes in Peyer's patches and intraepithelium of adult C57BL/6 mice during resolution of C. parvum infection. Resistance to initial severe infection was associated with CD4+alpha beta+IFN-gamma+ lymphocytes, and eventual resolution of infection was associated with CD4+alpha beta+IL-4+ lymphocytes. Analysis of cytokine expression following in vitro stimulation with C. parvum Ags during resolution of infection demonstrated consistent increases in CD4+alpha beta+IL-4+ lymphocytes, but not CD4+alpha beta+IFN-gamma+ lymphocytes. The relevance of CD4+alpha beta+IL-4+ lymphocytes in protection against C. parvum was then evaluated in C57BL/6 IL-4 gene knockout mice (IL-4(-/-)). Adult IL-4(-/-) mice excreted oocysts in feces approximately 23 days longer than IL-4(+/+) mice. Further, anti-IFN-gamma mAb treatment increased the severity and the duration of infection in IL-4(-/-) mice compared with those in IL-4(+/+) mice. Together, the data demonstrated that IFN-gamma was important in the control of severity of infection, and either IFN-gamma or IL-4 accelerated termination of infection. However, neither IL-4 nor IFN-gamma was required for the final clearance of infection from the intestinal tract of adult mice.
成年C57BL/6小鼠对严重微小隐孢子虫感染的抵抗力依赖于CD4+αβ+TCR淋巴细胞。在本研究中，我们证明用抗IFN-γ单克隆抗体治疗使卵囊排泄延长了18天，而抗IL-4单克隆抗体使卵囊排泄比同型对照单克隆抗体治疗至少延长了11天。对治疗小鼠血清中抗IFN-γ单克隆抗体的比活性分析表明，IFN-γ在感染的消退期可能作用有限。在微小隐孢子虫感染消退期间，成年C57BL/6小鼠派尔集合淋巴结和上皮内的CD4+αβ+IFN-γ+和CD4+αβ+IL-4+淋巴细胞数量也有变化。对初始严重感染的抵抗力与CD4+αβ+IFN-γ+淋巴细胞相关，而感染的最终消退与CD4+αβ+IL-4+淋巴细胞相关。在感染消退期间，用微小隐孢子虫抗原体外刺激后对细胞因子表达的分析表明，CD4+αβ+IL-4+淋巴细胞持续增加，而CD4+αβ+IFN-γ+淋巴细胞则不然。然后在C57BL/6 IL-4基因敲除小鼠（IL-4(-/-)）中评估CD4+αβ+IL-4+淋巴细胞在抗微小隐孢子虫感染中的相关性。成年IL-4(-/-)小鼠粪便中卵囊排泄比IL-4(+/+)小鼠长约23天。此外，与IL-4(+/+)小鼠相比，抗IFN-γ单克隆抗体治疗增加了IL-4(-/-)小鼠感染的严重程度和持续时间。总之，数据表明IFN-γ在控制感染严重程度方面很重要，并且IFN-γ或IL-4均可加速感染的终止。然而，成年小鼠肠道感染的最终清除既不需要IL-4也不需要IFN-γ。
