Department of Medicine, University of Colorado Denver, Aurora, CO 80045, USA.
Respir Res. 2010 Dec 16;11(1):179. doi: 10.1186/1465-9921-11-179.
The presence of anti-endothelial cell antibodies and pathogenic T cells may reflect an autoimmune component in the pathogenesis of emphysema. Whether immune modulatory strategies can protect against the development of emphysema is not known.
Sprague Dawley rats were immunized with human umbilical vein endothelial cells (HUVEC) to induce autoimmune emphysema and treated with intrathymic HUVEC-injection and pristane. Measurements of alveolar airspace enlargement, cytokine levels, immuno histochemical, western blot analysis, and T cell repertoire of the lung tissue were performed.
The immunomodulatory strategies protected lungs against cell death as demonstrated by reduced numbers of TUNEL and active caspase-3 positive cells and reduced levels of active caspase-3, when compared with lungs from HUVEC-immunized rats. Immunomodulatory strategies also suppressed anti-endothelial antibody production and preserved CNTF, IL-1alpha and VEGF levels. The immune deviation effects of the intrathymic HUVEC-injection were associated with an expansion of CD4+CD25+Foxp3+ regulatory T cells. Pristane treatment decreased the proportion of T cells expressing receptor beta-chain, Vβ16.1 in the lung tissue.
Our data demonstrate that interventions classically employed to induce central T cell tolerance (thymic inoculation of antigen) or to activate innate immune responses (pristane treatment) can prevent the development of autoimmune emphysema.
抗内皮细胞抗体和致病性 T 细胞的存在可能反映了肺气肿发病机制中的自身免疫成分。免疫调节策略是否能预防肺气肿的发生尚不清楚。
用人脐静脉内皮细胞（HUVEC）免疫 Sprague Dawley 大鼠，诱导自身免疫性肺气肿，并进行胸内 HUVEC 注射和异辛烷处理。测量肺泡气腔扩大、细胞因子水平、免疫组织化学、Western blot 分析和肺组织 T 细胞库。
与 HUVEC 免疫大鼠的肺相比，免疫调节策略通过减少 TUNEL 和活性 caspase-3 阳性细胞的数量以及降低活性 caspase-3 的水平，保护了肺免受细胞死亡的影响。免疫调节策略还抑制了抗内皮抗体的产生，并维持了 CNTF、IL-1alpha 和 VEGF 水平。胸内 HUVEC 注射的免疫偏差效应与 CD4+CD25+Foxp3+调节性 T 细胞的扩张有关。异辛烷处理降低了肺组织中表达受体β链、Vβ16.1 的 T 细胞的比例。
我们的数据表明，经典地用于诱导中枢 T 细胞耐受（胸腺内抗原接种）或激活固有免疫反应（异辛烷处理）的干预措施可以预防自身免疫性肺气肿的发生。
