Nouzé Clémence, Pasquet Lise, van Meerwijk Joost P M
Tolerance and Autoimmunity Section, Institut National de la Santé et de la Recherche Médicale, U563, Toulouse, France.
Methods Mol Biol. 2011;707:187-96. doi: 10.1007/978-1-61737-979-6_12.
Regulatory T lymphocytes expressing CD4, high levels of CD25, and the transcription factor Foxp3 play a crucial role in the control of immune responses to self and nonself antigens. In contrast to immunosuppressive drugs currently used to treat immunopathology, these cells act in a very specific manner. Consequently, their clinical potential in the treatment of autoimmune disorders, inflammatory diseases, graft-versus-host disease, and allograft rejection is currently extensively studied in experimental animal models as well as in clinical trials. We have previously shown that appropriately in vitro stimulated CD4(+)CD25(high) regulatory T cells can be used to prevent rejection of bone marrow, skin, and heart allografts in the Mouse. We here describe the protocols used in our laboratory to isolate mouse regulatory T cells, to stimulate them in vitro in order to enrich in cells specific for donor-antigens, and to transplant bone marrow under cover of regulatory T cells. Thus, generated hematopoietic chimeras may subsequently be transplanted with solid tissues and organs from the same donor.
表达CD4、高水平CD25和转录因子Foxp3的调节性T淋巴细胞在控制对自身和非自身抗原的免疫反应中起关键作用。与目前用于治疗免疫病理学的免疫抑制药物不同,这些细胞以非常特定的方式发挥作用。因此,它们在治疗自身免疫性疾病、炎症性疾病、移植物抗宿主病和同种异体移植排斥反应方面的临床潜力目前正在实验动物模型以及临床试验中进行广泛研究。我们之前已经表明,体外适当刺激的CD4(+)CD25(高)调节性T细胞可用于预防小鼠骨髓、皮肤和心脏同种异体移植的排斥反应。我们在此描述了我们实验室用于分离小鼠调节性T细胞、体外刺激它们以富集供体抗原特异性细胞以及在调节性T细胞保护下移植骨髓的方案。因此,随后可以将产生的造血嵌合体与来自同一供体的实体组织和器官进行移植。