Major and minor histocompatibility antigens to NIMA: Prediction of a tolerogenic NIMA effect.

The immunologic effects of developmental exposure to non-inherited maternal antigens (NIMA) are heterogeneous, either tolerogenic or immunogenic. The role of minor histocompatibility antigens (MiHA) in NIMA effects is unknown. We have recently reported that the NIMA effect can be classified into two distinct reactivities, low and high responder, to NIMA in utero and during nursing depending on the degree of maternal microchimerism (MMc) and Foxp3 expression of peripheral blood CD4(+)CD25(+) cells after graft-versus-host disease (GVHD) induction. These reactivities were predictable before transplantation, using an MLR-ELISPOT (mixed lymphocyte reaction; enzyme-linked immunospot) assay by comparing the number of IFNγ-producing cells stimulated with NIMA. Moreover, this assay was also applicable in both major and minor NIMA-mismatched setting. These observations are clinically relevant and suggest that it is possible to predict the immunological tolerance to NIMA.