Microchimerism is strongly correlated with tolerance to noninherited maternal antigens in mice
Microchimerism is strongly correlated with tolerance to noninherited maternal antigens in mice
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DOI：
10.1182/blood-2009-03-213561
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发表时间：
2009-10-22
期刊：
影响因子：
20.3
通讯作者：
Burlingham, William J.
中科院分区：
文献类型：
--
作者：
Dutta, Partha;Molitor-Dart, Melanie;Burlingham, William J.
在小鼠和人类中，发育暴露于非遗传性母源抗原（NIMAs）的免疫效应是非常不同的。这种异质性可能反映了nima特异性T调节细胞（T- r）与T效应细胞（T- e）相对水平的差异。我们假设在成人体内维持nima特异性T-R细胞需要持续暴露于母体细胞和抗原（例如母体微嵌合[MMc]）。为了验证这一想法，我们使用了2种敏感的定量聚合酶链反应（qPCR）检测NIMA暴露的H2(b)小鼠不同器官中的MMc。100%的新生儿和大多数（61%）成人检测到MMc；NIMA（+）母亲的护理对于将MMc保存到成年至关重要。MMc在心脏、肺、肝和血液中最常见，但在未分离的淋巴组织中很少发现。然而，在脾脏分离的CD4（+）、CD11b（+）和CD11c（+）细胞亚群以及心脏的谱系阳性细胞中可检测到MMc。延迟型超敏反应（DTH）的抑制和体内淋巴细胞增殖与MMc水平相关，表明T-R与母体细胞植入之间存在联系。在新生儿没有通过母乳喂养暴露于NIMA的情况下，MMc丢失，这伴随着一些后代对NIMA的敏化，表明口服暴露在维持良好的T-R > T-E平衡方面的作用。[血液。2009;114:3578-3587]
In mice and humans, the immunologic effects of developmental exposure to non-inherited maternal antigens (NIMAs) are quite variable. This heterogeneity likely reflects differences in the relative levels of NIMA-specific T regulatory (T-R) versus T effector (T-E) cells. We hypothesized that maintenance of NIMA-specific T-R cells in the adult requires continuous exposure to maternal cells and antigens (eg, maternal microchimerism [MMc]). To test this idea, we used 2 sensitive quantitative polymerase chain reaction (qPCR) tests to detect MMc in different organs of NIMA(d)-exposed H2(b) mice. MMc was detected in 100% of neonates and a majority (61%) of adults; nursing by a NIMA(+) mother was essential for preserving MMc into adulthood. MMc was most prevalent in heart, lungs, liver, and blood, but was rarely detected in unfractionated lymphoid tissues. However, MMc was detectable in isolated CD4(+), CD11b(+), and CD11c(+) cell subsets of spleen, and in lineage-positive cells in heart. Suppression of delayed type hypersensitivity (DTH) and in vivo lymphoproliferation correlated with MMc levels, suggesting a link between T-R and maternal cell engraftment. In the absence of neonatal exposure to NIMA via breastfeeding, MMc was lost, which was accompanied by sensitization to NIMA in some offspring, indicating a role of oral exposure in maintaining a favorable T-R > T-E balance. (Blood. 2009; 114:3578-3587)