Microchimerism is strongly correlated with tolerance to noninherited maternal antigens in mice

In mice and humans, the immunologic effects of developmental exposure to non-inherited maternal antigens (NIMAs) are quite variable. This heterogeneity likely reflects differences in the relative levels of NIMA-specific T regulatory (T_R) versus T effector (T_E) cells.We hypothesized that maintenance of NIMA-specific TR cells in the adult requires continuous exposure to maternal cells and antigens (eg, maternal microchimerism [MMc]). To test this idea, we used 2 sensitive quantitative polymerase chain reaction (qPCR) tests to detect MMc in different organs of NIMA^d-exposed H2^b mice. MMc was detected in 100% of neonates and a majority (61%) of adults; nursing by a NIMA⁺ mother was essential for preserving MMc into adulthood. MMc was most prevalent in heart, lungs, liver, and blood, but was rarely detected in unfractionated lymphoid tissues. However, MMc was detectable in isolated CD4⁺, CD11b⁺, and CD11c⁺ cell subsets of spleen, and in lineage-positive cells in heart. Suppression of delayed type hypersensitivity (DTH) and in vivo lymphoproliferation correlated with MMc levels, suggesting a link between T_R and maternal cell engraftment. In the absence of neonatal exposure to NIMA via breastfeeding, MMc was lost, which was accompanied by sensitization to NIMA in some offspring, indicating a role of oral exposure in maintaining a favorable T_R > T_E balance.