Khosrotehrani Kiarash, Leduc Michèle, Bachy Véronique, Nguyen Huu Sau, Oster Michèle, Abbas Aicha, Uzan Serge, Aractingi Sélim
Université Pierre et Marie Curie, Paris VI, EA4053, and Assistance Publique-Hôpitaux de Paris, France.
J Immunol. 2008 Jan 15;180(2):889-97. doi: 10.4049/jimmunol.180.2.889.
T lymphocytes of fetal origin found in maternal circulation after gestation have been reported as a possible cause for autoimmune diseases. During gestation, mothers acquire CD34+CD38+ cells of fetal origin that persist decades. In this study, we asked whether fetal T and B cells could develop from these progenitors in the maternal thymus and bone marrow during and after gestation. RAG-/--deficient female mice (Ly5.2) were mated to congenic wild-type Ly5.1 mice (RAG+/+). Fetal double-positive T cells (CD4+CD8+) with characteristic TCR and IL-7R expression patterns could be recovered in maternal thymus during the resulting pregnancies. We made similar observations in the thymus of immunocompetent mothers. Such phenomenon was observed overall in 12 of 68 tested mice compared with 0 of 51 controls (p=0.001). T cells could also be found in maternal spleen and produced IFN-gamma in the presence of an allogenic or an Ag-specific stimulus. Similarly, CD19+IgM+ fetal B cells as well as plasma Igs could be found in maternal RAG-/- bone marrow and spleen after similar matings. Our results suggest that during gestation mothers acquire fetal lymphoid progenitors that develop into functional T cells. This fetal cell microchimerism may have a direct impact on maternal health.
妊娠后在母体循环中发现的源自胎儿的T淋巴细胞被报道可能是自身免疫性疾病的一个原因。在妊娠期间，母亲会获得源自胎儿的CD34+CD38+细胞，这些细胞会持续数十年。在本研究中，我们探究了在妊娠期间及之后，胎儿的T细胞和B细胞是否能从母体胸腺和骨髓中的这些祖细胞发育而来。将RAG-/-缺陷雌性小鼠（Ly5.2）与同基因野生型Ly5.1小鼠（RAG+/+）交配。在随后的妊娠期间，可在母体胸腺中回收具有特征性TCR和IL-7R表达模式的胎儿双阳性T细胞（CD4+CD8+）。我们在具有免疫活性的母亲的胸腺中也观察到了类似现象。在68只受试小鼠中，共有12只出现了这种现象，而51只对照小鼠中无一出现（p=0.001）。在母体脾脏中也能发现T细胞，并且在同种异体或抗原特异性刺激存在的情况下产生γ干扰素。同样，在类似交配后的母体RAG-/-骨髓和脾脏中可发现CD19+IgM+胎儿B细胞以及血浆免疫球蛋白。我们的结果表明，在妊娠期间母亲获得了发育为功能性T细胞的胎儿淋巴祖细胞。这种胎儿细胞微嵌合现象可能会对母体健康产生直接影响。
