Microchimerism in cord blood: Mother as anticancer drug

Maternal microchimerism (MMc) in cord blood (CB) caused by the exchange of cells at the maternal–fetal interface was first described in 1995 by Hall et al. (1). To the many known immunologic consequences of maternal–fetal cell exchange and particularly, CB MMc must now be added yet another consequence: the antitumor immunotherapeutic effect of CB transplants. Surprisingly, this effect seems to be due at least in part, to rare maternal T cells contained therein. Because HLA loci are highly polymorphic and mothers and fathers are generally HLA heterozygous, the offspring are nearly always HLA mismatched with the mother for at least one of the antigens encoded by inherited paternal haplotypes at the HLA loci—HLA-A,B,C (class I) and HLA-DR,DQ,DP (class II). Because of homozygosity at certain HLA loci—for example, if the offspring is HLA-A2,A2—the inherited paternal antigen (IPA; in this case, A2) will not present a target HLA-A alloantigen to the mother's T and B lymphocytes. (Note that the analysis in this study did not evaluate IPAs that are minor histocompatibility antigens that may also be bound as peptides to HLA-A2 and presented to mother's minor H antigen-specific T cells; however, typing for these loci is still in its infancy, whereas HLA typing is relatively advanced.) Similarly, from the neonate's point of view, maternal homozygosity at a given locus (for example, if the mother is B62, B62) means that the B locus noninherited maternal antigen (NIMA; in this case B62) will not present a target for its T cells. However, if one knows the complete HLA-A,B,DR typing of the mother and offspring, one can usually identify heterozygous HLA loci encoding IPA and NIMA target antigens that could potentially stimulate an alloreactive T-cell response. Thus, the maternal–fetal interface at birth is an arena with diverse and sometimes opposing players; it is occupied, …