Anti-CD3 antibody decreases inflammation and improves outcome in a murine model of Pneumocystis pneumonia.
Anti-CD3 antibody decreases inflammation and improves outcome in a murine model of Pneumocystis pneumonia.
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DOI：
10.4049/jimmunol.0901864
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发表时间：
2010-01-01
期刊：
影响因子：
--
通讯作者：
Gigliotti F
中科院分区：
文献类型：
--
作者：
Bhagwat SP;Wright TW;Gigliotti F
肺孢子虫引起的T细胞介导的免疫应答在肺孢子虫肺炎（PcP）的肺损伤和功能障碍中起关键作用。感染前CD 4+和CD 8 + T细胞耗竭的小鼠尽管进行性肺部感染，但仍明显免受PcP相关呼吸缺陷和死亡的影响。然而，尚未确定抗体介导的T细胞功能破坏在已经显示疾病临床症状的小鼠中的治疗效果。因此，使用PcP相关免疫重建炎性综合征的鼠模型来评估当在疾病发作后施用时，泛T细胞分子CD 3的抗体是否有效降低PcP的严重程度。与接受对照抗体的小鼠相比，接受抗CD 3抗体的小鼠在治疗后一周内表现出快速和显著的停止PcP相关的肺功能下降，并且存活率显著提高。抗CD 3处理小鼠的生理改善与肺灌洗液中回收的CD 4+和CD 8 + T细胞数量的显著减少相关。无论小鼠是否也接受甲氧苄啶-磺胺甲恶唑抗生素治疗，抗CD 3的有效性都会被注意到。这些数据表明，单克隆抗体介导的T细胞功能的破坏可能是一种特异性和有效的连续治疗，以快速逆转正在进行的病理性免疫反应发生在积极的PcP。因此，抗人CD 3单克隆抗体OKT 3，这是已经在临床上使用，有可能被开发为一个PcP的免疫治疗。
The T cell-mediated immune response elicited by Pneumocystis plays a key role in pulmonary damage and dysfunction during Pneumocystis pneumonia (PcP). Mice depleted of CD4+ and CD8+ T cells prior to infection are markedly protected from PcP-related respiratory deficit and death despite progressive lung infection. However, the therapeutic effectiveness of antibody-mediated disruption of T cell function in mice already displaying clinical symptoms of disease has not been determined. Therefore, a murine model of PcP-related immune reconstitution inflammatory syndrome was used to assess whether antibody to the pan-T cell molecule CD3 is effective for reducing the severity of PcP when administered after the onset of disease. Mice that received anti-CD3 antibody exhibited a rapid and dramatic halt in the PcP-associated pulmonary function decline within one week post-treatment, and a striking enhancement of survival rate compared to mice receiving control antibody. Physiological improvement in anti-CD3 treated mice was associated with a significant reduction in the number of CD4+ and CD8+ T cells recovered in lung lavage fluid. This effectiveness of anti-CD3 was noted whether or not the mice also received antibiotic therapy with trimethoprim-sulfamethoxazole. These data suggest that monoclonal antibody-mediated disruption of T cell function may represent a specific and effective adjunctive therapy to rapidly reverse the ongoing pathological immune response occurring during active PcP. Thus, the anti-human CD3 monoclonal antibody OKT3, which is already in clinical use, has the potential to be developed as an adjunctive therapy for PcP.
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15.3
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