Ichinohe Tatsuo, Maruya Etsuko, Saji Hiroh
Department of Hematology/Oncology, Graduate School of Medicine, Kyoto University, Japan.
Int J Hematol. 2002 Oct;76(3):229-37. doi: 10.1007/BF02982792.
During pregnancy, fetal hematopoietic cells carrying paternal human leukocyte antigens (HLA) migrate into maternal circulation, and, vice versa, maternal nucleated cells can be detected in fetal organs and umbilical cord blood, indicating the presence of bidirectional cell traffic between mother and fetus. By taking advantage of fluorescence in-situ hybridization or polymerase chain reaction-based techniques, researchers recently found that postpartum persistence of such reciprocal chimerism was common among healthy individuals and may sometimes cause tissue chimerism. Although the biological significance of long-lasting feto-maternal microchimerism is unknown, a number of investigations have suggested its association with the development of "autoimmune" diseases such as systemic sclerosis. However, the very common presence of feto-maternal microchimerism among subjects without any autoimmune attack may allow us the more appealing hypothesis that it is an indicator for the acquired immunological hyporesponsiveness to noninherited maternal or fetal HLA antigens. An offspring's tolerance to noninherited maternal antigens has been clinically suggested by the retrospective analysis of renal transplantations or haploidentical hematopoietic stem cell transplantations, and whether postpartum mothers can tolerate paternally derived fetal antigens is an intriguing question. Although an exact linkage between microchimerism and transplantation tolerance is yet to be elucidated, long-term acceptance of a recipient's cell in the donor may have a favorable effect on preventing the development of severe graft-versus-host disease, and the donor cell microchimerism in the recipient might facilitate the graft acceptance. If this concept holds true, HLA-mismatched hematopoietic stem cell transplantation would be more feasible among haploidentical family members mutually linked with feto-maternal microchimerism. Further studies are warranted to investigate the potential role of feto-maternal microchimerism in human transplantation medicine.
在孕期，携带父源人类白细胞抗原（HLA）的胎儿造血细胞会迁移至母体循环，反之，在胎儿器官和脐带血中也能检测到母源有核细胞，这表明母胎之间存在双向细胞流通。利用基于荧光原位杂交或聚合酶链反应的技术，研究人员最近发现，产后这种相互嵌合现象在健康个体中很常见，有时可能导致组织嵌合。虽然持久的母婴微嵌合现象的生物学意义尚不清楚，但多项研究表明其与系统性硬化症等“自身免疫性”疾病的发生有关。然而，在没有任何自身免疫攻击的个体中母婴微嵌合现象非常普遍，这使我们可以提出一个更具吸引力的假说，即它是对非遗传的母源或胎儿HLA抗原获得性免疫低反应性的一个指标。肾移植或单倍体造血干细胞移植的回顾性分析已从临床上提示子代对非遗传母源抗原具有耐受性，产后母亲是否能耐受父源胎儿抗原是一个有趣的问题。虽然微嵌合现象与移植耐受性之间的确切联系尚待阐明，但受者细胞在供者体内的长期留存可能对预防严重移植物抗宿主病的发生有积极作用，而受者体内的供者细胞微嵌合现象可能会促进移植物的接受。如果这一概念成立，那么在存在母婴微嵌合现象的单倍体家庭成员之间进行HLA不匹配的造血干细胞移植将更可行。有必要进一步研究母婴微嵌合现象在人类移植医学中的潜在作用。
