Papin J, Brennand A, Arbore G, Hohenstein B, Kamvissi V, Kemper C, Bornstein S R
Department of Endocrinology and Diabetes, Division of Diabetes and Nutritional Sciences, King's College London, London SE5 9NU, UK; Faculty of Medicine Carl Gustav Carus, Fetscherstraße 74, 01307, Dresden, Germany.
Department of Endocrinology and Diabetes, Division of Diabetes and Nutritional Sciences, King's College London, London SE5 9NU, UK; Faculty of Medicine Carl Gustav Carus, Fetscherstraße 74, 01307, Dresden, Germany.
Atheroscler Suppl. 2017 Nov;30:238-245. doi: 10.1016/j.atherosclerosissup.2017.05.046. Epub 2017 Jun 3.
Lipoprotein-apheresis (LA) is a therapeutic approach used against severe forms of dyslipidemia in patients who are non-responders or intolerant to pharmacological treatments. However, little is known about the potential pleiotropic effects of LA, particularly regarding the immune system and its regulation. Thus, in an attempt to analyse the potential effects of dyslipidemia and LA on the regulation of CD4 T cells activation and lineage differentiation, we compared the CD4 T cells cytokines secretion profiles of dyslipidemic patients before and after LA with the profiles observed in healthy donors.
CD4 T cells were isolated from 5 LA patients and 5 healthy donors and activated with anti-CD3 or anti-CD3 + anti-CD46 antibodies. The supernatants were collected after 36 h incubation and levels of secreted cytokines analysed by flow cytometry.
Our results revealed a deep remodelling of CD4 T cells cytokines secretion patterns in dyslipidemic patients compared to healthy donors, as reflected by a 15 times higher IFN-γ secretion rate after CD3 + CD46 co-activation in dyslipidemic patients after LA compared to healthy subjects and 8 times higher after CD3 activation alone (p = 0.0187 and p = 0.0118 respectively). Moreover, we demonstrated that LA itself also modifies the phenotype and activation pattern of CD4 T-cells in dyslipidemic patients.
These observations could be of fundamental importance in the improvement of LA columns/systems engineering and in developing new therapeutic approaches regarding dyslipidemia and associated pathologies such as atherosclerosis and type 2 diabetes.
脂蛋白分离术（LA）是一种用于治疗对药物治疗无反应或不耐受的严重血脂异常患者的治疗方法。然而，关于LA潜在的多效性作用，尤其是对免疫系统及其调节的影响，人们了解甚少。因此，为了分析血脂异常和LA对CD4 T细胞活化和谱系分化调节的潜在影响，我们比较了血脂异常患者LA前后CD4 T细胞细胞因子分泌谱与健康供体中的情况。
从5名LA患者和5名健康供体中分离出CD4 T细胞，并用抗CD3或抗CD3 +抗CD46抗体激活。孵育36小时后收集上清液，通过流式细胞术分析分泌的细胞因子水平。
我们的结果显示，与健康供体相比，血脂异常患者的CD4 T细胞细胞因子分泌模式发生了深刻重塑，这表现为LA后血脂异常患者在CD3 + CD46共激活后IFN-γ分泌率比健康受试者高15倍，单独CD3激活后高8倍（分别为p = 0.0187和p = 0.0118）。此外，我们证明LA本身也会改变血脂异常患者CD4 T细胞的表型和激活模式。
这些观察结果对于改进LA柱/系统工程以及开发针对血脂异常和相关疾病（如动脉粥样硬化和2型糖尿病）的新治疗方法可能具有至关重要的意义。
