Ungar B L, Kao T C, Burris J A, Finkelman F D
Department of Preventive Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD 20814.
J Immunol. 1991 Aug 1;147(3):1014-22.
Cryptosporidium is a protozoan parasite that can cause chronic life-threatening diarrhea in immunocompromised persons. Host immune responses are poorly understood, an impediment to development of effective therapy. In mice, normal adult BALB/c animals resist infection whereas chronic symptomatic cryptosporidiosis develops in adult nude mice and in neonatally infected BALB/c mice treated with anti-CD4 mAb. To define further the immune defects that allow mice to be infected with Cryptosporidium, adult BALB/c mice were treated with cytolytic anti-CD4 or anti-CD8 or with neutralizing anti-IFN-gamma or anti-IL-2 mAb. Chronic infection, manifested by continuous shedding of sparse but statistically significant numbers of oocysts, occurred with anti-CD4 +/- anti-CD8 mAb treatment although anti-CD8 mAb treatment alone did not allow infection. Treatment with anti-IFN-gamma mAb greatly enhanced oocyst shedding but infection was self-limited. Treatment with a combination of anti-CD4 and anti-IFN-gamma mAb permitted both chronic infection and shedding of large numbers of oocysts. Furthermore mice treated initially with anti-CD4 mAb showed a substantial increase in oocyst shedding when later treated with anti-IFN-gamma mAb; and mice treated initially with both mAbs showed a decline in oocyst shedding when anti-IFN-gamma mAb was stopped. Anti-IFN-gamma mAb treatment of congenitally athymic adult BALB/c mice led to an approximately a 75-fold increase in oocyst shedding. Treatment of adult BALB/c mice with anti-IL-2 mAb did not permit Cryptosporidium infection. These results suggest that redundant immunologic mechanisms limit Cryptosporidium infection such that both CD4+ cells and IFN-gamma are required to prevent initiation of infection whereas either alone can limit the extent (IFN-gamma) or duration (CD4+ T cells) of infection. They also suggest that production of IFN-gamma by a non-T cell contributes to host immunity.
隐孢子虫是一种原生动物寄生虫，可在免疫功能低下的人群中引起危及生命的慢性腹泻。目前对宿主免疫反应的了解甚少，这阻碍了有效治疗方法的开发。在小鼠中，正常成年BALB/c动物能抵抗感染，而成年裸鼠以及用抗CD4单克隆抗体处理过的新生感染BALB/c小鼠则会发生慢性症状性隐孢子虫病。为了进一步明确导致小鼠感染隐孢子虫的免疫缺陷，对成年BALB/c小鼠进行了溶细胞性抗CD4或抗CD8抗体处理，或用中和性抗干扰素-γ或抗白细胞介素-2单克隆抗体处理。用抗CD4 +/- 抗CD8单克隆抗体处理后出现了慢性感染，表现为持续排出数量稀少但具有统计学意义的卵囊，尽管单独使用抗CD8单克隆抗体处理不允许感染。用抗干扰素-γ单克隆抗体处理大大增加了卵囊排出，但感染是自限性的。联合使用抗CD4和抗干扰素-γ单克隆抗体处理可导致慢性感染并排出大量卵囊。此外，最初用抗CD4单克隆抗体处理过的小鼠，后来用抗干扰素-γ单克隆抗体处理时，卵囊排出量大幅增加；而最初同时用两种单克隆抗体处理的小鼠，停用抗干扰素-γ单克隆抗体后卵囊排出量下降。对先天性无胸腺的成年BALB/c小鼠用抗干扰素-γ单克隆抗体处理导致卵囊排出量增加约75倍。用抗白细胞介素-2单克隆抗体处理成年BALB/c小鼠不允许隐孢子虫感染。这些结果表明，多种免疫机制限制了隐孢子虫感染，因此需要CD4+细胞和干扰素-γ共同作用来预防感染的起始，而单独一种则可以限制感染的程度（干扰素-γ）或持续时间（CD4+ T细胞）。它们还表明非T细胞产生的干扰素-γ有助于宿主免疫。
