Microchimerism is the exchange of cells between the mother and the fetus during pregnancy. Low level of these cells is found persistence in the offspring decades after delivery. The number of persisting maternal cells has been associated with several autoimmune disorders such as systemic sclerosis, juvenile dermatomyositis or diabetes. However the precise role of the maternal cells in these disorders remains unclear.
Based on recent experimental work, we hypothesized that maternal allogeneic T cells acquired during fetal life modify the offspring’s response to self by perturbing mechanisms of immune tolerance. Our aim was to document the capacity of alloreactive maternal cells acquired during pregnancy to predispose to immune disorders in the offspring.
To investigate if maternal cells have a role in auto-immunity in the progeny, we crossed balb/c males to either C57Bl/6 or to RAG1KO (on C57Bl/6 background) females. This allowed us to compare 2 groups of mice with the same genetic background that respectively had (B6:Bc) or had not (RAG:Bc) received maternal alloreactive T cells. Despite being of the same background RAG:Bc mice had an expanded hematopoietic system at 3 and 6 weeks and 18 months.This was particularly true for CD8+ T cells. The relative frequency of regulatory T cells was conserved at 6 weeks. Contact-hypersensitivity skin reactions were stronger in Rag:Bc mice. Finally, in aged mice, we observed a skin phenotype consisting of depilation and thickening. Histology of back-skin revealed superficial and mostly deep fibrosis with a loss of muscle and fat layers. Only 4 out of 15 (26%) mice were fibrotic in B6:Bc group compared to 10 out of 15 (66%) among the Rag:Bc offspring (p<0.05). The intensity of the fibrosis was also superior in the Rag:Bc group.
This work highlights the major and long term influence of peri-natal events on the immune compartment, immune and tissue responses and may serve as a basis for our understanding of systemic sclerosis.