Burlingham William J
a Department of Surgery; Division of Transplantation ; University of Wisconsin ; Madison , WI , USA.
Chimerism. 2014;5(3-4):63-7. doi: 10.1080/19381956.2015.1082026. Epub 2015 Dec 17.
It has become increasingly clear that the immune system of viviparous mammals is much more in the business of acquiring tolerance to non-self antigens, than it is in rejecting cells that express them (for a recent review, highlighting the role of Treg cells, see ref. (1) ). It is also clear that both self-tolerance, and acquired tolerance to non-self is a dynamic process, with a natural ebb and flow. As has been often said of an effective team defense in sports, tolerance will "bend but does not break." How microchimerism, defined as the presence of extremely rare [1/10(4)-1/10(6)] cells of a genetically different individual, can induce either new immunogenetic pressures that push self-tolerance to the breaking point, or alternatively, provide relief from pre-existing immunogenetic risk, preventing development of autoimmune disease, remains a mystery. Indeed, the inability to directly correlate DNA-level microchimerism detected in blood samples by qPCR, with naturally occurring regulation to minor H and MHC alloantigens expressed by the rare cells themselves, has been frustrating to researchers in this field. (2) [Haynes, W.J. et al, this issue] However, recent developments in the areas of transplantation and reproductive immunology offer clues to how the effects of microchimerism can be amplified, and how a disproportionate immune impact might occur from a very limited cell source.
越来越明显的是，胎生哺乳动物的免疫系统更多地致力于获得对非自身抗原的耐受性，而不是排斥表达这些抗原的细胞（关于最近一篇强调调节性T细胞作用的综述，见参考文献(1)）。同样明显的是，自身耐受性以及对非自身的获得性耐受性都是一个动态过程，有自然的起伏。正如人们常说的体育比赛中有效的团队防守，耐受性会“弯曲但不会断裂”。微嵌合体被定义为存在极其罕见的[1/10(4)-1/10(6)]个基因不同个体的细胞，它如何能引发新的免疫遗传压力，将自身耐受性推向临界点，或者相反，减轻先前存在的免疫遗传风险，预防自身免疫性疾病的发生，仍然是一个谜。事实上，通过定量聚合酶链反应（qPCR）在血样中检测到的DNA水平微嵌合体，无法与罕见细胞自身表达的次要组织相容性抗原（minor H）和主要组织相容性复合体（MHC）同种异体抗原的自然调节直接相关联，这一直令该领域的研究人员感到沮丧。(2) [海恩斯，W.J.等人，本期] 然而，移植和生殖免疫学领域的最新进展为微嵌合体的作用如何被放大，以及非常有限的细胞来源如何产生不成比例的免疫影响提供了线索。
