Pereira Claudia Barreto, Palaci Moises, Leite Olavo H M, Duarte Alberto J S, Benard Gil
Laboratório de Investigação Médica, Unidade 56, Departmento de Dermatologia, Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil.
Microbes Infect. 2004 Jan;6(1):25-33. doi: 10.1016/j.micinf.2003.10.007.
Cell-mediated immunity, leading to Mycobacterium tuberculosis (Mtb)-constraining granuloma formation, is the major component of host defense against tuberculosis and is regulated by the balance of cytokines secreted mostly by mononuclear phagocytes and lymphocytes. To better understand the role of monocytes in the regulation of the immune response against pulmonary tuberculosis, we examined IL-10, IL-12 and TNF-alpha release by monocytes from healthy purified protein derivative (PPD) reactors and pulmonary tuberculosis patients with or without systemic reactions (e.g., fever, weight loss, asthenia). Our study shows that, probably as a result of in vivo priming by circulating antigens, monocytes from patients, especially those with systemic manifestations, have a biased ex vivo cytokine secretion, with high IL-10 and TNF-alpha but low IL-12, in contrast with PPD reactors. Higher spontaneous IL-10 and TNF-alpha release persisted when monocytes were co-cultured with autologous lymphocytes. Challenge of patients' monocytes with a virulent Mtb strain led to a further enhancement of IL-10 and TNF-alpha, but not of IL-12. When lymphocytes were added to these cultures, IL-10 and TNF-alpha elevation persisted and, in the patients with a systemic reaction, both IL-12 and IFN-gamma were significantly reduced compared to PPD reactors. Intragroup comparisons revealed that in the patients with systemic reactions, the lymphocyte-monocyte interaction resulted in a positive feedback for IL-10 secretion, while in the patients without systemic reaction and PPD reactors, the feedback was positive for IL-12 secretion. Thus, in tuberculosis, there appears to exist a relationship between the immunological findings and the distinct clinical manifestations.
细胞介导的免疫反应可导致结核分枝杆菌（Mtb）受限性肉芽肿的形成，是宿主抵御结核病的主要组成部分，并且受主要由单核吞噬细胞和淋巴细胞分泌的细胞因子平衡所调节。为了更好地理解单核细胞在调节针对肺结核的免疫反应中的作用，我们检测了来自健康的纯化蛋白衍生物（PPD）反应者以及有或无全身反应（如发热、体重减轻、乏力）的肺结核患者的单核细胞释放的白细胞介素-10（IL-10）、白细胞介素-12（IL-12）和肿瘤坏死因子-α（TNF-α）。我们的研究表明，可能由于循环抗原在体内的致敏作用，患者的单核细胞，尤其是那些有全身表现的患者，离体后细胞因子分泌存在偏差，与PPD反应者相比，IL-10和TNF-α水平高而IL-12水平低。当单核细胞与自体淋巴细胞共培养时，IL-10和TNF-α的自发释放持续升高。用强毒力的Mtb菌株刺激患者的单核细胞导致IL-10和TNF-α进一步升高，但IL-12未升高。当向这些培养物中加入淋巴细胞时，IL-10和TNF-α持续升高，并且在有全身反应的患者中，与PPD反应者相比，IL-12和干扰素-γ（IFN-γ）均显著降低。组内比较显示，在有全身反应的患者中，淋巴细胞-单核细胞相互作用导致IL-10分泌的正反馈，而在无全身反应的患者和PPD反应者中，反馈对IL-12分泌是正性的。因此，在结核病中，免疫表现与不同的临床表现之间似乎存在关联。
