Chimerism

During gestation, maternal cells traffic to the fetus leading to the natural phenomenon of microchimerism. Although their persistence in offspring has been associated with several autoimmune disorders, the precise role of maternal cells in these disorders remains unclear. We aimed to evaluate whether alloreactive maternal T cells could directly trigger a graft-vs.-host like reaction or indirectly influence the development of the offspring's regulatory T cells (Treg) favoring autoimmunity. In a specific breeding strategy, we recently reported that maternal allogeneic T cells changed fetal Treg development and their quantities in mesenteric lymph nodes, leading to early signs of inflammation in the gut later in life...

Increased levels of non-inherited maternal HLA alleles have been detected in the periphery of children with type 1 diabetes and an increased frequency of maternal cells have been identified in type 1 diabetes pancreas. It is now clear that the phenotype of these cells is pancreatic, supporting the hypothesis that maternal cells in human pancreas are derived from multipotent maternal progenitors. Here we hypothesize how increased levels of maternal cells could play a role in islet autoimmunity.

Allogeneic hematopoietic stem cell transplantation (HSCT) is a widely applied treatment for disorders mainly involving the hematopoietic system. The success of this treatment depends on many different patient- and donor-specific factors. Based on higher CD34+ yields and superior clinical outcomes associated with the use of male donors, males are generally seen as the preferred HSCT donor. In addition, female donors are notorious for bearing memory type lymphocytes induced by previous pregnancies; such alloimmune cells may provoke unwanted immune reactions such as graft-vs...

Fetal microchimerism (FMc) is predicted to promote the fitness of the fetus and maternal microchimerism (MMc) to promote the fitness of the mother. Offspring and mothers benefit from each other's health. Therefore, microchimeric cells should usually not be harmful to their host. However, the evolutionary interests of mothers and offspring diverge when there is competition among siblings for maternal investment. Fetal cells in mothers' bodies could benefit their own offspring at the expense of its sibs by promoting lactogenesis or by extending the interbirth interval...

Microchimerism represents a condition where one individual harbors genetically distinct cell populations, and the chimeric population constitutes <1% of the total number of cells. The most common natural source of microchimerism is pregnancy. The reciprocal cell exchange between a mother and her child often leads to the stable engraftment of hematopoietic and non-hematopoietic stem cells in both parties. Interaction between cells from the mother and those from the child may result in maternal immune cells becoming sensitized to inherited paternal alloantigens of the child, which are not expressed by the mother herself...

Fetal cells persist in mothers for decades after delivery: in a phenomenon called fetal microchimerism. While persistent fetal cells were first implicated in autoimmune disease, parallel studies in animal and human pregnancy now suggest that microchimeric fetal cells play a role in the response to tissue injury. The aim of this study was to investigate the impact of fetal microchimeric cells in the adult wound, using caesarean section (CS) as a model of wound healing in pregnancy. XY-FISH (fluorescence in situ hybridization) and immunostaining was used in multiple tissue sections from CS skin biopsies from 70 women, to locate, quantitate and characterize microchimeric male presumed-fetal cells...

The etiology of biliary atresia (BA) is unknown; however, the liver histology is similar to that observed in immune-mediated hepatic disorders. Liver fibrosis in BA progresses even after bile drainage has been achieved by the Kasai operation. Maternal microchimerism has been purported to play a part in the pathogenesis of BA as well as certain autoimmune diseases. However, the role of maternal cells has not yet been determined in BA. Specifically, it is unknown whether these maternal cells function as maternal effector T lymphocytes, or targets or bystanders...

Long-term maintenance of immune components with defined specificity, without antigen is the hallmark feature of immunological memory. However, there are fundamental differences in how memory CD8(+) compared with CD4(+) T cells are maintained. After complete antigen elimination, CD8(+) T cells can persist as a self-renewing numerically stable cell population, and therefore satisfy the most stringent definition of "memory." Comparatively, CD4(+) T cell maintenance is considerably less stable, often requiring low-level antigen persistence or antigenic reminders...

Although pregnancy-associated microchimerism is known to exist in humans, its clinical significance remains unclear. Fetal microchimerism has been documented in rhesus monkeys, but the trafficking and persistence of maternal cells in the monkey fetus and infant have not been fully explored. To investigate the frequency of maternal microchimerism in the rhesus monkey (Macaca mulatta), a real-time polymerase chain reaction (PCR) strategy was developed and validated to target polymorphic major histocompatibility complex (MHC) gene sequences...

No abstract text is available yet for this article.

Microchimerism (MC), transplacental acquisition of allogeneic cells from the mother (maternofetal MC) or from the fetus (fetomaternal MC) has been in the focus of research recently. Amplicons using Y-chromosome specific SRY and DYS14 sequences have been used as markers to trace cells from a male fetus in the mother. The sensitivity of these markers in formaldehyde fixed paraffin embedded samples, however, is less than optimal. To study chimerism in breast cancer we took advantage of the evolutionary history of the Y chromosome and designed amplicons on gene repeats to generate additive PCR signals...

Transfusion therapy is complicated by the production of alloantibodies to antigens present in the donor and lacking in the recipient through the poorly-understood but likely multi-factorial process of alloimmunization. The low prevalence of alloimmunization in transfused patients (6.1%) (1) suggests that processes central to immunologic tolerance may be operating in the vast majority of transfused patients who do not produce alloantibodies. Using RhD as a prototype, evidence is reviewed that the ability to make antibodies to red blood cell (RBC) antigens may result in part from immunologic tolerance acquired in utero...

In utero hematopoietic cellular transplantation (IUHCT) holds great promise for the treatment of congenital diseases of cellular dysfunction such as sickle cell disease, immunodeficiency disorders and inherited metabolic disorders. However, repeated failures in clinical cases of IUHCT that do not involve an immunodeficiency disease force a closer examination of the fetal immune system. While the mechanisms regulating T cell tolerance have been previously studied, the educational mechanisms leading to NK cell tolerance in prenatal chimeras remain unknown...

Trogocytosis has been identified as a mechanism of cell communication between immune cells. Unlike the more common receptor-ligand signaling, trogocytosis results in the transfer of intact and functional surface proteins between cells. For example, antigen presenting cells in contact with T cells exchange proteins which results in the T-cell acquiring antigen presentation capabilities. This allows for the newly activated T cells to stimulate other T cells thus amplifying the immune response. We have recently demonstrated that during allogeneic hematopoietic stem cell transplantation the donor cells obtain recipient MHC class I proteins by trogocytosis...

Fetal microchimerism (FMC) has been described to have a range of effects on health and disease. Y-chromosomal DNA has been detected in Golden Retrievers suggesting persistent FMC. In that report, nine dogs had evidence of microchimerism without prior pregnancy. To further understand this finding, a dam with prior male live births giving birth to her fourth litter of puppies, all females, was evaluated for FMC along with two of her daughters. All three female dogs had evidence of Y-chromosomal DNA in their blood...

Fetal cells transfer to the mother during pregnancy and can persist long-term as microchimerism. Acquisition of microchimerism may also occur during pregnancy loss, either miscarriage or pregnancy termination. Because nearly half of all pregnancies end in loss, we recently investigated the magnitude of fetal cell transfer during pregnancy loss and whether obstetric clinical factors impacted cell transfer. Prospective measurement of fetal cellular microchimerism before and after miscarriage and termination of pregnancy demonstrated a significant transfer of fetal cells in these pregnancies, with higher concentrations of fetal microchimerism in pregnancy termination vs...

Autoimmune thyroid diseases (AITD) show a female predominance, with an increased incidence in the years following parturition. Fetal microchimerism has been suggested to play a role in the pathogenesis of AITD. However, only the presence of fetal microchimeric cells in blood and in the thyroid gland of these patients has been proven, but not an actual active role in AITD. Is fetal microchimerism harmful for the thyroid gland by initiating a Graft versus Host reaction (GvHR) or being the target of a Host versus Graft reaction (HvGR)? Is fetal microchimerism beneficial for the thyroid gland by being a part of tissue repair or are fetal cells just innocent bystanders in the process of autoimmunity? This review explores every hypothesis concerning the role of fetal microchimerism in AITD...

Accurate quantification of chimerism and microchimerism is proving to be increasingly valuable for hematopoietic cell transplantation as well as non-transplant conditions. However, methods that are available to quantify low-level chimerism lack accuracy. Therefore, we developed and validated a method for quantifying chimerism based on digital PCR technology. We demonstrate accurate quantification that far exceeds what is possible with analog qPCR down to 0.01% with the potential to go even lower. Also, this method is inherently more informative than qPCR...

Multipotent mesenchymal stem/stromal cells (MSCs) have been extensively used as a transplantable cell source for regenerative medicine and immunomodulatory therapy. Specifically in allogeneic hematopoietic stem cell transplantation (HSCT), co-transplantation or post-transplant infusion of MSCs derived from bone marrow (BM) of non-self donors has been implicated in accelerating hematopoietic recovery, ameliorating graft-vs.-host disease, and promoting tissue regeneration. However, irrespective of the use of MSC co-administration, post-transplant chimerism of BM-derived MSCs after allogeneic HSCT has been reported to remain of host origin, suggesting that the infused donor MSCs are immunologically rejected or not capable of long-term engraftment in the host microenvironment...

No abstract text is available yet for this article.