Pregnancy allows the transfer and differentiation of fetal lymphoid progenitors into functional T and B cells in mothers.
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.
Khosrotehrani
Kiarash
K
Université Pierre et Marie Curie, Paris VI, EA4053, and Assistance Publique-Hôpitaux de Paris, France. kiarash.khosrotehrani@tnn.aphp.fr
Leduc
Michèle
M
Bachy
Véronique
V
Nguyen Huu
Sau
S
Oster
Michèle
M
Abbas
Aicha
A
Uzan
Serge
S
Aractingi
Sélim
S
D000818:Animals; D000906:Antibodies / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology*; D002465:Cell Movement; D005260:Female; D053686:Fetal Stem Cells / Q000166:cytology* / Q000276:immunology; D018398:Homeodomain Proteins / Q000235:genetics; D054503:Lymphoid Progenitor Cells / Q000166:cytology* / Q000276:immunology; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D008822:Mice, Transgenic; D011247:Pregnancy / Q000276:immunology*; D013154:Spleen / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D013950:Thymus Gland / Q000276:immunology
D000906:Antibodies; D018398:Homeodomain Proteins; C064658:RAG-1 protein