Charité-University Medicine Berlin, Campus Benjamin Franklin, Hindenburgdamm, Berlin, Germany.
Hum Immunol. 2010 Apr;71(4):366-71. doi: 10.1016/j.humimm.2010.01.005. Epub 2010 Jan 25.
Infection with Toxoplasma gondii (TG) presents in some individuals as a self-limited disease with a predominant lymphadenopathy characterized by prominent B-cell activation. As this is in contrast to the in vitro based concept of a T(h)1-immune response against TG, we investigated native lymphoid tissue and peripheral blood of a patient with serologic evidence of toxoplasmosis to verify which cells show T(h)1-response features. High-level expression of T-bet in monocytoid B-cells, in germinal center B-cells, and in a lesser amount in T cells could be demonstrated by immunohistochemistry. In vitro stimulation of lymph node cells with either TG, staphylococcus enterotoxin B, or phorbol 12-myristate 13-acetate/ionomycin revealed an interferon-gamma expression in T-bet(+) B cells only in the patient and not in controls. Similar results were found for T-bet(+) T cells which were also present in controls. CD4(+) peripheral blood cells stimulated with TG antigens showed a TG-specific but attenuated T(h)1-reactivity in the patient associated with a reduced expression of IL-2 when compared with controls. We conclude that the pathogenesis and course of toxoplasmic lymphadenopathy is based on a T(h)1-cell defect, which becomes compensated by the B cells mounting a T(h)1-like immune response.
刚地弓形虫(Toxoplasma gondii,TG)感染在某些个体中表现为自限性疾病,以显著的 B 细胞激活为特征的主要淋巴结病。由于这与基于体外的针对 TG 的 Th1 免疫反应的概念相反,我们研究了一名具有血清学证据的弓形虫病患者的固有淋巴组织和外周血,以验证哪些细胞显示出 Th1 反应特征。通过免疫组织化学可以证明单核细胞样 B 细胞、生发中心 B 细胞和 T 细胞中高水平的 T-bet 表达。用 TG、肠毒素 B 或佛波醇 12-肉豆蔻酸 13-乙酸盐/离子霉素体外刺激淋巴结细胞,仅在患者中而不在对照中发现 T-bet+ B 细胞中表达干扰素-γ。在对照中也存在 T-bet+ T 细胞,也发现了类似的结果。与对照相比,用 TG 抗原刺激的 CD4+外周血细胞显示出 TG 特异性但减弱的 Th1 反应,其伴随 IL-2 的表达降低。我们得出结论,弓形虫淋巴结病的发病机制和病程基于 Th1 细胞缺陷,该缺陷通过 B 细胞产生 Th1 样免疫反应得到代偿。