Influence of Maternal-Fetal Histocompatibility and MHC Zygosity on Maternal Microchimerism

Abstract

To investigate the relationship between maternal-fetal histocompatibility and maternal microchimerism, we developed a sensitive quantitative PCR assay for the neomycin resistance gene (neoR), and, in a mouse model system, used neoR as a noninherited maternal allele marker of maternal cells to detect and quantitate maternal microchimerism in tissues of neoR−/− N2 backcross progeny of (neoR+/−)F1 females mated with neoR−/− males. Using this approach, we obtained evidence for the presence of chimeric maternal cells in the brain, spleen, and thymus of all weanling and adult mice so tested. The numbers of chimeric maternal cells present in the spleen did not differ significantly from those in the thymus regardless of age or maternal-fetal histocompatibility. At all ages, brain tissue had higher level of maternal microchimerism than lymphoid tissue in mice MHC identical with their mothers, but the levels were similar in mice MHC disparate with their mothers. The levels of chimeric maternal cells in both brain and lymphoid tissue of mice with homozygous syngenicity and maternal allogenicity were similar, and tended to be higher than tissue-specific levels in mice with either combined maternal-fetal allogenicity or heterozygous syngenicity. Thus, MHC homozygous progeny had higher levels of maternal microchimerism than MHC heterozygous progeny. We conclude that normal mice possess small numbers of maternal cells in spleen, thymus, brain, and probably most other tissues, and that maternal-fetal histocompatibility influences the levels of these cells by mechanisms related to MHC zygosity of the progeny.

Maternal microchimerism in peripheral blood in type 1 diabetes and pancreatic islet β cell microchimerism

“…Other possibilities include shared environmental factors as well as the possibility that a sibling may be more likely to share HLA and other genes with the mother than an unrelated individual. In a murine model, some histocompatibility relationships were found to correlate with increased levels of MMc (26). We were unable to explore this question because our methods were based on HLA incompatibility.…”

Maternal T cells limit engraftment after in utero hematopoietic cell transplantation in mice

“…In humans, maternal-fetal cellular trafficking may contribute to fetal immune development and maternal-fetal tolerance, inducing the fetus to develop Tregs against maternal antigens (19). Changes in the levels of maternal-fetal cellular trafficking have been reported to correspond with maternal-fetal histocompatibility in the mouse model, suggesting that cellular trafficking has implications for maternal-fetal tolerance (37,40).…”

Developmental Exposure to Noninherited Maternal Antigens Induces CD4+ T Regulatory Cells: Relevance to Mechanism of Heart Allograft Tolerance

“…We have shown previously that both in utero and oral exposure are required for the NIMA effect seen in this highly immunogenic murine heart allograft model (13). In utero exposure to maternal soluble Ags and cells, and the establishment of maternal microchimerism, could allow for NIMA presentation in the thymus, thus allowing for the development of natural T R cells (8,33,34). Oral administration of Ag has previously been shown to expand CD4 ϩ CD25 ϩ T R cells which are able to suppress DTH reactions (35), and under more physiological conditions like nursing, it has been shown that oral tolerance is largely mediated through mucosal induction of adaptive CD4 ϩ T R cells producing IL-10 and TGF-␤ that can suppress the systemic response to the same Ag (36,37).…”