Transplantation

Michael Eikmans

Leiden University Medical Center, The Netherlands

Microchimerism can cause immune recognition between mother and fetus. Differences in human leukocyte antigen (HLA) genes between two hosts is a main driver of immune reactions. The child inherits one set of HLA genes from the mother and one from the father. The mother may develop immunity by forming antibodies and effector- and regulatory T cells, which are specific against the inherited paternal antigens (IPA) of the fetus. Vice versa, T cells from the fetus may show reactivity to non-inherited maternal antigens (NIMA).

Likewise, exposure of a recipient to a transplanted organ or cells from a genetically different individual leads to immune reactions. Previous studies have emphasized the possible consequence of microchimerism for outcome of transplantation performed later in life. For instance, immune recognition by the pregnant woman may lead to HLA antibody development, forming a hurdle when a transplant is given containing HLA antigens to which those antibodies are directed to. Alternatively, maternal exposure during pregnancy in the womb leads to immune tolerance. If a patient, having developed tolerance toward the NIMA, is offered a donor kidney containing a mismatched antigen that is the same as the NIMA, there is no significant negative impact on transplant outcome.

In this lecture I focus on maternal microchimerism (mMC) in the fetus. Umbilical cord blood (UCB) from the newborn can be used as a source for cell transplantation in patients suffering from leukemia. Clinical studies provided indirect evidence that mMC cells in fetal blood mediate graft-versus-leukemia effects in the recipient after UCB transplantation. Attempts for enriching these cells are discussed along with questions including: which cell types are these chimeric cells? How are these chimeric cells maintained and not cleared by the host’s immune system? Why would these cells not directly attack host cells, but would exert alloreactivity in a recipient?