Porciello Nicla, Kunkl Martina, Tuosto Loretta
Sir William Dunn School of Pathology, University of Oxford, Oxford, OX1 3RE, UK.
Department of Biology and Biotechnology Charles Darwin, Sapienza University, Rome, Italy.
F1000Res. 2018 May 30;7. doi: 10.12688/f1000research.14046.1. eCollection 2018.
Regulation of immune responses is critical for ensuring pathogen clearance and for preventing reaction against self-antigens. Failure or breakdown of immunological tolerance results in autoimmunity. CD28 is an important co-stimulatory receptor expressed on T cells that, upon specific ligand binding, delivers signals essential for full T-cell activation and for the development and homeostasis of suppressive regulatory T cells. Many mouse models have been used for understanding the role of CD28 in the maintenance of immune homeostasis, thus leading to the development of CD28 signaling modulators that have been approved for the treatment of some autoimmune diseases. Despite all of this progress, a deeper understanding of the differences between the mouse and human receptor is required to allow a safe translation of pre-clinical studies in efficient therapies. In this review, we discuss the role of CD28 in tolerance and autoimmunity and the clinical efficacy of drugs that block or enhance CD28 signaling, by highlighting the success and failure of pre-clinical studies, when translated to humans.
免疫反应的调节对于确保病原体清除和防止针对自身抗原的反应至关重要。免疫耐受的失败或破坏会导致自身免疫。CD28是一种在T细胞上表达的重要共刺激受体，在与特定配体结合后，传递对于T细胞完全活化以及抑制性调节性T细胞的发育和稳态必不可少的信号。许多小鼠模型已被用于了解CD28在维持免疫稳态中的作用，从而促成了已被批准用于治疗某些自身免疫性疾病的CD28信号调节剂的开发。尽管取得了所有这些进展，但仍需要更深入地了解小鼠和人类受体之间的差异，以便将临床前研究安全地转化为有效的治疗方法。在这篇综述中，我们通过强调临床前研究转化为人体试验时的成功与失败，讨论CD28在耐受性和自身免疫中的作用以及阻断或增强CD28信号的药物的临床疗效。
