Sahlolbei Maryam, Azangou-Khyavy Mohammadreza, Khanali Javad, Khorsand Babak, Shiralipour Aref, Ahmadbeigi Naser, Madjd Zahra, Ghanbarian Hossein, Ardjmand Alireza, Hashemi Seyed Mahmoud, Kiani Jafar
Department of Molecular Medicine, Faculty of Advanced Technologies in Medicine, Iran University of Medical Sciences (IUMS), Tehran, Iran.
Oncopathology Research Center, Iran University of Medical Sciences, Tehran, Iran.
Heliyon. 2023 Sep 1;9(9):e19763. doi: 10.1016/j.heliyon.2023.e19763. eCollection 2023 Sep.
Recent evidence suggests that B cells and autoantibodies have a substantial role in the pathogenesis of Multiple sclerosis. T cells could be engineered to express chimeric autoantibody receptors (CAARs), which have an epitope of autoantigens in their extracellular domain acting as bait for trapping autoreactive B cells. This study aims to assess the function of designed CAAR T cells against B cell clones reactive to the myelin basic protein (MBP) autoantigen.
T cells were transduced to express a CAAR consisting of MBP as the extracellular domain. experimental autoimmune encephalomyelitis (EAE) was induced by injecting MBP into mice. The cytotoxicity, proliferation, and cytokine production of the MBP-CAAR T cells were investigated in co-culture with B cells.
MBP-CAAR T cells showed higher cytotoxic activity against autoreactive B cells in all effector-to-target ratios compared to Mock T cell (empty vector-transduced T cell) and Un-T cells (un-transduced T cell). In co-cultures containing CAAR T cells, there was more proliferation and inflammatory cytokine release as compared to Un-T and Mock T cell groups.
Based on these findings, CAAR T cells are promising for curing or modulating autoimmunity and can be served as a new approach for clone-specific B cell depletion therapy in multiple sclerosis.
最近有证据表明，B细胞和自身抗体在多发性硬化症的发病机制中起重要作用。可以对T细胞进行工程改造，使其表达嵌合自身抗体受体（CAAR），该受体在其细胞外结构域具有自身抗原表位，可作为捕获自身反应性B细胞的诱饵。本研究旨在评估设计的CAAR T细胞对与髓鞘碱性蛋白（MBP）自身抗原反应的B细胞克隆的功能。
转导T细胞以表达由MBP作为细胞外结构域组成的CAAR。通过向小鼠注射MBP诱导实验性自身免疫性脑脊髓炎（EAE）。在与B细胞共培养中研究MBP-CAAR T细胞的细胞毒性、增殖和细胞因子产生。
与模拟T细胞（空载体转导的T细胞）和未转导T细胞（未转导的T细胞）相比，MBP-CAAR T细胞在所有效应细胞与靶细胞比例下对自身反应性B细胞均表现出更高的细胞毒性活性。与未转导T细胞和模拟T细胞组相比，在含有CAAR T细胞的共培养物中，有更多的增殖和炎性细胞因子释放。
基于这些发现，CAAR T细胞有望用于治疗或调节自身免疫，可作为多发性硬化症中克隆特异性B细胞耗竭疗法的一种新方法。
