Baldwin William M, Su Charles A, Shroka Thomas M, Fairchild Robert L
aDepartment of Immunology, Lerner Research Institute, Cleveland Clinic bSchool of Health Sciences, Cleveland State University, Cleveland, Ohio, USA.
Curr Opin Organ Transplant. 2014 Oct;19(5):525-30. doi: 10.1097/MOT.0000000000000113.
Experimental models have contributed enormously to basic immunology. However, the use of reductionist experiments has produced results that are not always successfully translated into the clinic. Recently, incorporation of more realistic clinical parameters in experimental designs has produced new insights relevant to cardiac transplantation.
Experiments in mice have provided crucial insights into the concept that T cell responses to pathogens generate memory cells with cross-reactive specificities for histocompatibility antigens. These memory T cells are resistant to current immunosuppressive strategies. Memory T cells infiltrate grafts within hours after transplantation, and grafts subjected to clinically relevant periods of cold ischemia are more susceptible to injury by this cellular infiltrate. Early immune responses now can be investigated with improved 'humanized' mice. Mice with multiple knock-in genes for human cytokines support development of human monocytes, macrophages and natural killer cells in increased numbers and with better function.
Better and more clinically relevant experimental designs are providing animal models tailored to address clinic exigencies.
实验模型对基础免疫学做出了巨大贡献。然而，简化论实验的结果并不总能成功转化到临床应用中。最近，在实验设计中纳入更符合实际的临床参数，为心脏移植带来了新的见解。
小鼠实验为T细胞对病原体的反应产生对组织相容性抗原有交叉反应特异性的记忆细胞这一概念提供了关键见解。这些记忆T细胞对当前的免疫抑制策略具有抗性。记忆T细胞在移植后数小时内浸润移植物，经历临床相关冷缺血时间的移植物更容易受到这种细胞浸润的损伤。现在可以通过改良的“人源化”小鼠来研究早期免疫反应。携带多种人类细胞因子敲入基因的小鼠能支持更多数量且功能更好的人类单核细胞、巨噬细胞和自然杀伤细胞的发育。
更好且更符合临床实际的实验设计正在提供适合解决临床紧急情况的动物模型。
