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* Université Pierre et Marie Curie, Paris VI, EA4053, Paris, France;
Assistance Publique-Hôpitaux de Paris, Service de Dermatologie, Hôpital Tenon, Paris, France;
Institut National de la Santé et de la Recherche Médicale Unité 712, Hôpital Saint-Antoine, Paris, France; and
Assistance Publique-Hôpitaux de Paris, Service de Biochimie, Hôpital Tenon, Paris, France
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-
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.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This work was supported by the Université Pierre et Marie Curie (Paris VI) BQR 2005 Grant, the Fondation pour la Recherche Médicale INE20050303543, the Société Française de Dermatologie, the Assistance Publique-Hôpitaux de Paris CRC04026, and the Association Française contre les Myopathies G12670A/S01975, Paris, France. M.L. was supported by the French Ministry of Education.
2 K.K. and M.L. contributed equally and should be considered as first authors.
3 Address correspondence and reprint requests to Dr. Kiarash Khosrotehrani, Service de Dermatologie, Hôpital Tenon, 4 rue de la Chine, 75020 Paris, France. E-mail address: kiarash.khosrotehrani{at}tnn.aphp.fr
4 Abbreviations used in this paper: EGFP, enhanced GFP; DP, double positive; SP, single positive.
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