Peripheral Tissue Antigen Display by Mesenchymal Stem Cells

描述（由申请人提供）：推动本项目的基本原理是，体内存在已知表达外周组织抗原（pTAs）并诱导体内对自身反应性淋巴细胞耐受的天然细胞。我们发现MSCs也表达这些pTA，并且与其他表达pTA的细胞不同，MSCs在体外加工过程中可以维持这种表达。我们假设MSCs表达自身抗原对自身免疫性疾病模型中细胞移植的治疗效果至关重要，因此可能适合体外监测/优化以创建定制的细胞治疗。目的是评估体外和体内MSCs免疫反应中pTA表达的相关性，并在抗原特异性肠道自身免疫模型治疗期间对这些细胞移植物进行成像。长期目标是评估这种独特的MSCs抗原呈递形式作为一种治疗模式的使用，并从本质上创造一种基于抗原特异性干细胞移植物的新药。

DESCRIPTION (provided by applicant): The rationale driving this project is that there are natural cells in the body that are known to express peripheral tissue antigens (pTAs) and induce tolerance to self-reactive lymphocytes in vivo. We have discovered that MSCs also express these pTAs and can maintain this expression during ex vivo processing unlike other pTA expressing cells. We hypothesize that the expression of self antigens by MSCs is essential for the therapeutic efficacy of cell transplants in models of autoimmune disease, and therefore may be amenable to ex vivo monitoring/optimization to create a tailored cell therapy. The objectives are to evaluate the relevance of pTA expression in the immune response to MSCs, both in vitro and in vivo, and image these cell grafts during the treatment of an antigen-specific model of intestinal autoimmunity. The long-term goal is to evaluate this use of a unique form of antigen presentation by MSCs as a therapeutic mode of action and essentially create a new drug class based on antigen-specific stem cell grafts.