Immune CD8(+) T Cells Prevent Reactivation of Toxoplasma gondii Infection in the Immunocompromised Host

Toxoplasma gondii remains a serious cause of morbidity and mortality in individuals that are immunosuppressed, patients with AIDS in particular. The cellular immune response, especially by gamma interferon (IFN-γ)-producing CD8(+) T cells, is an essential component of protective immunity against the parasite. In the present study the role of CD8(+) T cells during the reactivation of Toxoplasma infection in an immunocompromised murine model was evaluated. Chronically infected mice were challenged with LP-BM5 virus, and the kinetics of CD8(+) T-cell function was studied. At 10 weeks after viral infection, mice showed obvious signs of systemic illness and began to die. At this stage, CD8(+) T cells were unresponsive to antigenic stimulation and unable to kill Toxoplasma-infected targets. IFN-γ production by the CD8(+) T cells from dual-infected animals reached background levels, and a dramatic fall in the frequency of precursor cytotoxic T lymphocytes was observed. Histopathological analysis of the tissues demonstrated signs of disseminated toxoplasmosis as a result of reactivation of infection. However, treatment of the dual-infected animals with immune CD8(+) T cells at 5 weeks post-LP-BM5 challenge prevented the reactivation of toxoplasmosis, and mice continued to live. Our study for the first time demonstrates a therapeutic role for CD8(+) T cells against an opportunistic infection in an immunocompromised state.

刚地弓形虫（Toxoplasma gondii）仍是引发免疫功能低下人群发病乃至死亡的重要病原体，尤以艾滋病（AIDS）患者为甚。细胞免疫应答，尤其是产γ干扰素（gamma interferon, IFN-γ）的CD8阳性T细胞（CD8(+) T cells），是对抗该寄生虫的保护性免疫的核心组成部分。本研究针对免疫缺陷小鼠模型，评估了CD8阳性T细胞在弓形虫感染复燃过程中的作用。研究人员对慢性感染弓形虫的小鼠施以LP-BM5病毒攻毒，并对CD8阳性T细胞功能的动力学变化展开研究。病毒感染10周后，小鼠显现出明显的全身性疾病征象并开始死亡。此阶段，CD8阳性T细胞对抗原刺激无应答，且无法杀伤被弓形虫感染的靶细胞；双重感染小鼠的CD8阳性T细胞所分泌的γ干扰素水平降至背景水平，前体细胞毒性T淋巴细胞的频率亦出现显著下降。组织病理学分析显示，感染复燃引发了播散性弓形虫病。不过，在LP-BM5病毒攻毒后5周，向双重感染小鼠输注免疫性CD8阳性T细胞，可阻断弓形虫病的复燃，小鼠得以存活。本研究首次证实了CD8阳性T细胞在免疫缺陷状态下对抗机会性感染的治疗功效。