The effect of an anti-CD3 monoclonal antibody on bleomycin-induced lymphokine production and lung injury
The effect of an anti-CD3 monoclonal antibody on bleomycin-induced lymphokine production and lung injury
复制标题
DOI：
10.1164/ajrccm.154.1.8680680
复制
发表时间：
1996-07-01
影响因子：
24.7
通讯作者：
Kradin, RL
中科院分区：
文献类型：
--
作者：
Sharma, SK;Maclean, JA;Kradin, RL
气管内给药博来霉素（BLM）可引起C57BL/6小鼠急性肺损伤。注射0.1 U BLM后，肺和淋巴结的CD3（+）淋巴细胞和t -辅助性1 （Th1）淋巴因子白介素-2 （IL-2）和干扰素- γ (ifn - γ)的产生增加。肺淋巴细胞产生Th2细胞因子IL-4减少。腹腔注射大鼠抗尿CD3（YCD3）单克隆抗体（mAb）可阻断肺CD3（+）细胞的积累长达14天，并在整个治疗过程中有效抑制肺淋巴细胞的IL-2和IL-4，但不抑制ifn - γ的产生。YCD3治疗可抑制淋巴结细胞分泌上述所有淋巴因子。与使用同种型匹配的对照单抗治疗的小鼠相比，给予YCD3可减少BLM给药后的肺纤维化并提高生存率（p < 0.01）。在BLM后第5-7天开始使用YCD3治疗也可减少肺纤维化并显著降低死亡率（p < 0.02）。我们得出结论，BLM在肺中产生潜在致命的纤维炎症反应，该反应通过拮抗体内CD3（+）细胞的功能活性而显着减弱。
Acute lung injury was produced in C57BL/6 mice by the intratracheal (i.t.) administration of bleomycin (BLM). Following injection of 0.1 U BLM, CD3(+) lymphocytes and the production of the T-helper-1 (Th1) lymphokines interleukin-2 (IL-2) and interferon-gamma (IFN-gamma) were increased in lung and lymph nodes. The production of the Th2 cytokine IL-4 by lung lymphocytes was decreased. Intraperitoneal (i.p.) injection of a rat antimurine CD3 (YCD3) monoclonal antibody (mAb) blocked the accumulation of pulmonary CD3(+) cells for up to 14 d and effectively suppressed IL-2 and IL-4 but not IFN-gamma production by lung lymphocytes throughout the protocol. Secretion of all of the above lymphokines by lymph node cells was inhibited by YCD3 treatment. Administration of YCD3 diminished pulmonary fibrosis and increased survival (p < 0.01) following BLM administration compared with mice treated with an isotype-matched control mAb. Initiating treatment with YCD3 at Days 5-7 following BLM also decreased pulmonary fibrosis and significantly reduced mortality (p < 0.02). We conclude that BLM yields a potentially lethal fibroinflammatory response in the lung that is markedly diminished by antagonizing the functional activities of CD3(+) cells in vivo.