Zea Arnold H, Culotta Kirk S, Ali Juzar, Mason Carol, Park Hae-Joon, Zabaleta Jovanny, Garcia Luis F, Ochoa Augusto C
Stanley S. Scott Cancer Center, Louisiana State University Health Sciences Center, New Orleans, LA 70112, USA.
J Infect Dis. 2006 Nov 15;194(10):1385-93. doi: 10.1086/508200. Epub 2006 Oct 4.
The protective immune response against Mycobacterium tuberculosis relies both on antigen-presenting cells and on T lymphocytes. In patients with different forms of tuberculosis, varying degrees of T cell function--ranging from positive delayed-type hypersensitivity, in asymptomatic infected healthy individuals, to the absence of the response, in patients with miliary or pulmonary tuberculosis (PTB)--have been reported. The decreased expression of CD3zeta reported in T cells from patients with either cancer or leprosy has provided possible explanations for the altered immune response observed in these diseases.
The present study aimed to compare the expression of CD3zeta , nuclear transcription factor- kappa B (NF- kappa B), arginase activity, and cytokine production in 20 patients with PTB, in 20 tuberculin-positive asymptomatic subjects, and in 14 tuberculin-negative control subjects.
Compared with those in tuberculin (purified protein derivative)-negative control subjects, peripheral-blood T lymphocytes from patients with active PTB had significantly (P < .001) decreased expression of CD3zeta and absence of the p65/p50 heterodimer of NF- kappa B. These alterations were reversed only in patients who responded to treatment. Also reported here for the first time is that the presence of arginase activity in peripheral-blood mononuclear-cell lysates of patients with PTB parallels high production of interleukin-10.
The presence of arginase could, in part, explain the decreased expression of CD3zeta . These findings provide a novel mechanism that may explain the T cell dysfunction observed in patients with PTB.
针对结核分枝杆菌的保护性免疫反应既依赖于抗原呈递细胞，也依赖于T淋巴细胞。在患有不同形式结核病的患者中，已报道了不同程度的T细胞功能——从无症状感染的健康个体中的阳性迟发型超敏反应，到粟粒性或肺结核（PTB）患者中的无反应状态。在癌症或麻风病患者的T细胞中报道的CD3ζ表达降低，为这些疾病中观察到的免疫反应改变提供了可能的解释。
本研究旨在比较20例PTB患者、20例结核菌素阳性无症状受试者和14例结核菌素阴性对照受试者中CD3ζ、核转录因子-κB（NF-κB）的表达、精氨酸酶活性和细胞因子产生情况。
与结核菌素（纯化蛋白衍生物）阴性对照受试者相比，活动性PTB患者外周血T淋巴细胞的CD3ζ表达显著降低（P <.001），且不存在NF-κB的p65/p50异二聚体。这些改变仅在对治疗有反应的患者中得到逆转。本文首次报道的是，PTB患者外周血单个核细胞裂解物中精氨酸酶活性的存在与白细胞介素-10的高产生平行。
精氨酸酶的存在可能部分解释了CD3ζ表达的降低。这些发现提供了一种新机制，可能解释PTB患者中观察到的T细胞功能障碍。
