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Steven L Rosinski, Scott S Graves, Deborah A Higginbotham, Rainer Storb
This study tested whether an alloimmune response can occur in the marrow donor when infused or injected with leukocytes from their mixed chimeric transplant recipient. Two mixed chimeras were produced after conditioning with three Gray total body irradiation, donor marrow infusion, and post-grafting immunosuppression. The marrow donors were then repeatedly infused and injected with leukocytes from their respective chimeric recipient. A donor lymphocyte infusion (DLI) into their mixed chimeras had no effect, even after the experiments were repeated...
October 2, 2015: Chimerism
Jhade D Woodall, Mehmet C Uluer, Matthew T Chrencik, Arthur J Nam, Stephen T Bartlett, Rolf N Barth
The importance of further elucidating the properties surrounding microchimerism in various experi- mental models and clinical transplantation are limited by current techniques and the sensitivity of available platforms. Development of reliable methods and use routine use of microchimerism detection in clinical practice could guide clinical decision making regarding rejection, stable function, and tolerance.
October 2, 2015: Chimerism
Amanda Cecilie Müller, Marianne Antonius Jakobsen, Torben Barington, Allan Arthur Vaag, Louise Groth Grunnet, Sjurdur Frodi Olsen, Mads Kamper-Jørgensen
Male microchimerism, the presence of a small number of male cells, in women has been attributed to prior pregnancies. However, male microchimerism has also been reported in women with only daughters, in nulliparous women and prepubertal girls suggesting that other sources of male microchimerism must exist. The aim of the present study was to examine the presence of male microchimerism in a cohort of healthy nulliparous Danish girls aged 10-15 y using DNA extracted from cells from whole blood (buffy coats) and report the association with potential sources of male cells...
October 2, 2015: Chimerism
Houda Alachkar, Yusuke Nakamura
Haplo-cord transplant has emerged as a feasible and reliable approach for haematopoietic stem cell transplant in patients who are unable to find matched-donor. This approach provides fast myeloid recovery, low incidence of graft vs host disease (GVHD) and favorable graft versus leukemia (GVL) effects. T cell recovery plays an important role in preventing infectious complications; it also mediates the GVHD and the GVL effects. Here, we utilized a novel RNA-based sequencing approach to quantitatively characterize the T cell receptor (TCRs) repertoire in patients underwent haplo-cord transplant in comparison with those underwent matched-donor transplant...
July 3, 2015: Chimerism
Brian E McIntosh, Matthew E Brown
Immunocompromised mice are an essential tool for human xenotransplantation studies, including human haematopoietic stem cell (HSC) biology research. Over the past 35 years, there have been many advances in the development of these mouse models, offering researchers increasingly sophisticated options for creating clinically relevant mouse-human chimeras. This addendum article will focus on our recent development of the "NSGW" mouse, which, among other beneficial traits, is genetically modified to obviate the need for myeloablative irradiation of the animals...
April 3, 2015: Chimerism
Dixon B Kaufman
No abstract text is available yet for this article.
April 3, 2015: Chimerism
Aryn Martin
This article interweaves a history of Ray Owen's early work with a broader account of the conceptual landscape of immunology in the mid 1950's. In particular, Owen's openness to the very possibility of chimeric phenomena is recognized.
April 3, 2015: Chimerism
Samuel Strober
Tolerance to combined kidney and hematopoietic cell transplant has been achieved in humans after establishment of mixed chimerism allowing for the withdrawal of immunosuppressive drugs. The seminal contributions of Ray Owen provided the scientific basis for the human protocol.
April 3, 2015: Chimerism
Suzanne T Ildstad, Joseph Leventhal, Yujie Wen, Esma Yolcu
For over 50 y the association between hematopoietic chimerism and tolerance has been recognized. This originated with the brilliant observation by Dr. Ray Owen that freemartin cattle twins that shared a common placental blood supply were red blood cell chimeras, which led to the discovery that hematopoietic chimerism resulted in actively acquired tolerance. This was first confirmed in neonatal mice by Medawar et al. and subsequently in adult rodents. Fifty years later this concept has been successfully translated to solid organ transplant recipients in the clinic...
April 3, 2015: Chimerism
Tetsu Oura, Kiyohiko Hotta, A B Cosimi, Tatsuo Kawai
Mixed chimerism discovered in Freemartin cattle by Ray Owen 70 years ago paved the way for research on immune tolerance. Since his discovery, significant progress has been made in the effort to induce allograft tolerance via mixed chimerism in various murine models. However, induction of persistent mixed chimerism has proved to be extremely difficult in major histocompatibility complex mismatched humans. Chimerism induced in humans tends to either disappear or convert to full donor chimerism, depending on the intensity of the conditioning regimen...
April 3, 2015: Chimerism
Jeremy M Kinder, Tony T Jiang, James M Ertelt, Lijun Xin, Beverly S Strong, Aimen F Shaaban, Sing Sing Way
Compulsory exposure to genetically foreign maternal tissue imprints in offspring sustained tolerance to noninherited maternal antigens (NIMA). Immunological tolerance to NIMA was first described by Dr. Ray D. Owen for women genetically negative for erythrocyte rhesus (Rh) antigen with reduced sensitization from developmental Rh exposure by their mothers. Extending this analysis to HLA haplotypes has uncovered the exciting potential for therapeutically exploiting NIMA-specific tolerance naturally engrained in mammalian reproduction for improved clinical outcomes after allogeneic transplantation...
April 3, 2015: Chimerism
W John Haynes, Ewa Jankowska-Gan, Lynn Haynes, William J Burlingham
Long-term harmful effects of immunosuppressive drugs and chronic rejection are a persistent impetus to establish methods to induce immunological tolerance to allografts. PCR-based studies have found evidence that humans and other placental mammals can have prolonged extremely low levels of maternal cells as well as other non-self cells, referred to as microchimerism. The persistence of these cells suggests a mechanism for the maintenance of the regulatory T-cell (Treg) responses frequently detected in offspring to non-inherited maternal antigens...
2014: Chimerism
William J Burlingham
It has become increasingly clear that the immune system of viviparous mammals is much more in the business of acquiring tolerance to non-self antigens, than it is in rejecting cells that express them (for a recent review, highlighting the role of Treg cells, see ref. (1) ). It is also clear that both self-tolerance, and acquired tolerance to non-self is a dynamic process, with a natural ebb and flow. As has been often said of an effective team defense in sports, tolerance will "bend but does not break." How microchimerism, defined as the presence of extremely rare [1/10(4)-1/10(6)] cells of a genetically different individual, can induce either new immunogenetic pressures that push self-tolerance to the breaking point, or alternatively, provide relief from pre-existing immunogenetic risk, preventing development of autoimmune disease, remains a mystery...
2014: Chimerism
Kirsten A Thus, Roel A de Weger, Talitha A de Hoop, Valeria E Boers Trilles, Jürgen Kuball, Eric Spierings
Predicted indirectly recognizable HLA epitopes (PIRCHE) computationally predict donor T-cell recognition of mismatched-HLA derived peptides following allogeneic haematopoietic stem-cell transplantation (allo-HSCT), as is evidenced by the correlation between presence of HLA-DPB1-derived PIRCHE and the occurrence of graft-vs.-host disease (GVHD). Complete donor T-cell chimerism associates with an increased GVHD risk compared to mixed patient and donor chimerism. If the correlation between the presence of PIRCHE and GVHD occurrence is indeed mediated by donor T cells, the presence of donor T cells should be required to observe such a correlation...
2014: Chimerism
Marco Andreani, Monica Emma Gianolini, Manuela Testi, MariaRosa Battarra, Galluccio Tiziana, Aldo Morrone, Pietro Sodani, Guido Lucarelli, Maria-Grazia Roncarolo, Silvia Gregori
In a cohort of β-Thalassemia (β-Thal) transplanted with haploidentical-HSCT we identified one transplanted patient characterized by persistent mixed chimerism (PMC) for several months after HSCT. In this unique β-Thal patient we assessed the donor engraftment overtime after transplantation, the potential loss of the non-shared HLA haplotype, and the presence of CD49b(+)LAG-3(+) T regulatory type 1 (Tr1) cells, previously demonstrated to be associated with PMC after HLA-related HSCT for β-Thal. The majority of the patient's erythrocytes were of donor origin, whereas T cells were initially mostly derived from the recipient, no HLA loss, but an increased frequency of circulating Tr1 cells were observed...
2014: Chimerism
Valentina Cirello, Laura Fugazzola
Studies on both circulating and tissue fetal cell microchimerism (FCM) favored its protective role in thyroid cancer, consistent with findings in other malignancies. Nevertheless, scanty data were available on the possible impact on the outcome of the disease. We demonstrated that FCM has a positive effect on thyroid cancer presentation and outcome. We also excluded that the better clinical features observed were due to the effect of pregnancy per se. In conclusion, FCM may have not only a protective role toward the onset of thyroid cancer, but also a positive effect on its progression...
2014: Chimerism
Rena Hirani, Zsolt J Balogh, Natalie J Lott, Jeremy M Hsu, David O Irving
Despite the introduction of leukodepleted blood components, it has been shown that donor leukocyte engraftment (microchimerism) remains a long-term consequence of red blood cell (RBC) transfusion. The incidence of microchimerism may be affected by international disparities in blood processing methods or variations in transfusion practices. This study was conducted to determine the prevalence of microchimerism in Australian trauma patients. A secondary aim was to examine whether any patient complications correlated to the incidence of microchimerism...
2014: Chimerism
Hilary S Gammill, Mary D Stephenson, Tessa M Aydelotte, J Lee Nelson
Miscarriage is the most common pregnancy complication, and recurrent miscarriage (3 or more consecutive pregnancy losses) affects 1-5% of couples. Maternal-fetal exchange and the persistence of exchanged material as microchimerism appears to be disrupted in complicated pregnancies. We recently conducted a longitudinal cohort study of microchimerism in women with recurrent miscarriage. Our initial data raise multiple questions that require further investigation. Here, we review our data from this recent study and provide additional information regarding microchimerism in the granulocyte cell layer...
2014: Chimerism
Marta Wegorzewska, Tom Le, Qizhi Tang, Tippi C MacKenzie
Fetal surgery is a promising strategy to treat fetuses with severe congenital abnormalities but its clinical applications are often limited by preterm labor. In normal pregnancy, multiple mechanisms protect the semi-allogeneic fetus from attack by maternal T cells. Maternal microchimerism (the presence of maternal cells in the fetus) has been suggested to be one mechanism of maternal-fetal tolerance in that it exposes the fetus to non-inherited maternal antigens and leads to the generation of fetal regulatory T cells that can suppress a maternal T cell response...
2014: Chimerism
Maria Emilia Solano, Kristin Thiele, Ina Annelies Stelzer, Hans-Willi Mittrücker, Petra Clara Arck
Maternal microchimerism, which occurs naturally during gestation in hemochorial placental mammals upon transplacental migration of maternal cells into the fetus, is suggested to significantly influence the fetal immune system. In our previous publication, we explored the sensitivity of quantitative polymerase chain reaction and flow cytometry to detect cellular microchimerism. With that purpose, we created mixed cells suspensions in vitro containing reciprocal frequencies of wild type cells and cells positive for enhanced green fluorescent protein or CD45...
2014: Chimerism
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