Pregnancy Allows the Transfer and Differentiation of Fetal Lymphoid Progenitors into Functional T and B Cells in Mothers

Abstract

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-γ 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.

Specific maternal microchimeric T cells targeting fetal antigens in β cells predispose to auto-immune diabetes in the child

“…We have previously shown that fetal lymphoid progenitor cells enter the maternal thymus and develop into double positive and single positive thymocytes [10]. Their development in the maternal environment might explain their lack of reactivity toward maternal antigens.…”

“…We have previously demonstrated the transfer of fetal lymphoid progenitors to the mother and the development and activity of fetal OT2 cells in maternal thymus and spleen [10]. We therefore asked whether OT2 transgenic fetal T cells could react against maternal pancreatic islets expressing ovalbumin.…”

“…Elispot assays for g-interferon secretion were performed as previously described [10]. In each well 500,000 responder total splenocytes were incubated for 24 h in plates (Millipore, Molsheim, France) precoated with anti-g-IFN antibody (Becton Dickinson), in the presence of 100,000 syngenic bone-marrow derived dendritic cells loaded with various amounts of the ovalbumin peptide.…”

Microchimérisme fœtal : un bien ou un mal pour le fœtus et sa mère ?

“…Ces cellules T d'origine foetale pourraient compenser le dé ficit immunitaire en cas de dé faut du systè me immunitaire maternel. Dans le thymus maternel, les cellules T foetales ré actives vis-à -vis des antigè nes maternels subiraient une dé lé tion induisant une tolé rance aux antigè nes maternels [52]. La dé couverte ré cente de cellules suppressives T CD8+ spé cifiques des antigè nes HY chez la femme té moigne d'une maturation et de la mise en place d'une tolé rance vis-à -vis des antigè nes foetaux [53].…”

Microchimérisme fœtal : soi et non soi, finalement qui sommes-nous ?

“…En cas d'immunité maternelle déficiente, ces cellules T d'origine foetale compenseraient le déficit. Dans le thymus maternel, les cellules T foetales réactives vis-à-vis des allo-antigènes maternels subiraient une délétion induisant une tolérance aux antigènes maternels [68]. La découverte récente de cellules T CD8+ spécifiques des antigènes HY chez la femme témoigne d'une maturation et de la mise en place d'une tolérance vis-à-vis des antigènes foetaux [69].…”