Transmaternal cell flow leads to antigen-experienced cord blood

Donor parity no longer a barrier for female-to-male hematopoietic stem cell transplantation

“…13 It is however questionable if simply labeling a donor as being parous or nulliparous correctly reflects a sufficient difference in alloimmunization status. There is increasing evidence that women may already be exposed to HY antigens in early childhood, for instance through transmaternal flow of cells derived from an older male sibling 23 or from a twin brother who vanished in utero 24 ; both can lead to persistence of low levels of tissue-resident or circulating male sibling cells carrying HY antigens. 1 How the putatively lifelong presence of male microchimeric cells, in combination with mucosal exposure to male proteins in sexually active women, affects the adult female immune system had never been addressed.…”

Naturally acquired microchimerism

“…86 Interestingly, male chimerism is not necessarily restricted to women with male offspring, given that trans-maternal flow of male cells derived from a former pregnancy or from a twin sibling who died in utero can be transferred during a next pregnancy. 47,55,87 Consequently, female cord blood units may comprise functional T cells directed against alloantigens, which are not expressed by the mother but which have been encountered through trans-maternal cell flow of chimeric cells. 55 Likewise, the alloimmune T cell repertoire of multiparous women may contain considerable precursor frequencies of cells directed against the various mismatched HLA alleles expressed by either the maternal grandmother or by her offspring, or against mismatched minor histocompatibility antigens presented by shared HLA antigens.…”

“…Human fetal or maternal microchimeric cells can be found in circulating blood cells such as granulocytes, 51 lymphocytes, 52 monocytes, 53 and myeloid dendritic cells 54,55 as well as in organs and tissues 56 Using quantitative PCR technology for the detection of nonshared polymorphic HLA genes unique to mother-and fetus-derived cells, it was shown that adult women often carry multiple types of naturally acquired chimeric cells derived from different sources, i.e., from their mother and from their offspring. Addressing the prevalence of these two types of chimeric cells specifically within short-lived and continuously replenished cells of myeloid origin, Nelson and colleagues demonstrated that maternal microchimerism is actually more common in granulocytes obtained from adult females than fetal microchimerism.…”

We are all born as microchimera

“…11 Furthermore, induction of antigen specific T cells through transmaternal cell flow is not restricted to broadly expressed Y chromosome encoded minor H antigens, since T cell reactivity against hematopoietic restricted minor H antigens can be detected as well. More specifically, HA-1 H specific T cells from 2 HA-1 RR UCB of HA-1 RR mothers were isolated which specifically lysed HA-1 H peptide pulsed target cells.…”

“…Most of these explanations are educated guesses based on indirect evidence. In our recent paper, we identified male microchimerism in different leukocyte subsets in female umbilical cord blood (UCB) 11 which can only be explained by transmaternal passage. Whether these cells are derived from previous pregnancies or have survived in these mothers from birth onwards, has not been studied in detail yet.…”