Chimerism最新文献

{"title":"The role of pDC, recipient T(reg) and donor T(reg) in HSC engraftment: Mechanisms of facilitation.","authors":"Paul A Cardenas,&nbsp;Yiming Huang,&nbsp;Suzanne T Ildstad","doi":"10.4161/chim.2.3.17588","DOIUrl":"https://doi.org/10.4161/chim.2.3.17588","url":null,"abstract":"<p><p>Hematopoietic stem cell transplantation (HSCT) has been utilized for treatment of many hematologic malignancies, genetic and metabolic disorders, and hemoglobinopathies such as sickle cell disease and thalassemia. It also induces donor-specific tolerance to organ and tissue transplants. The widespread success of HSCT is hampered by the toxicities of immunosuppression and development of graft-versus-host disease (GVHD). The mechanism of induction of transplantation tolerance (reciprocal donor/host) is still an elusive challenge in allogeneic HSCT. An understanding of the mechanisms for induction of tolerance and the critical cells involved in this process has resulted in novel cell-based therapies poised to be translated to clinical application. The focus of this review is those cells of interest.Bone marrow-derived plasmacytoid dendritic cells induce naïve T cells to differentiate to become antigen-specific regulatory T cells (T(reg)), creating a milieu for the induction of transplantation tolerance. Recently, CD8(+)/TCR(-) facilitating cells (FC), a novel cell population in mouse bone marrow, have been shown to potently enhance engraftment of allogeneic HSC without causing GVHD. The predominant subpopulation of FC resembles plasmacytoid precursor dendritic cells. FC induce antigen-specific T(reg) in vivo. Notably, FC address one major concern that has prevented the implementation of T(reg) cell therapy in the clinic: to expand T(reg) and have them remain tolerogenic in vivo. FC are novel in that they induce an antigen-specific regulatory milieu in vivo. The discovery of FC has opened new alternatives to expanded criteria in bone marrow transplantation that were previously restricted to human leukocyte antigen-matched recipients. The focus of this review is to cover what is currently known about the mechanism of FC action in inducing tolerance and preventing GVHD and hostversus-graft reactivity. </p>","PeriodicalId":89114,"journal":{"name":"Chimerism","volume":"2 3","pages":"65-70"},"PeriodicalIF":0.0,"publicationDate":"2011-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3234357/pdf/chim0203_0065.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30320011","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Can maternal microchimeric cells influence the fetal response toward self antigens?","authors":"L. Leveque, K. Khosrotehrani","doi":"10.4161/chim.17589","DOIUrl":"https://doi.org/10.4161/chim.17589","url":null,"abstract":"The origins of autoimmunity are still elusive despite significant advances in immunology. There is cumulative evidence that, beyond simple genetics, the maternal environment plays a critical role in the development of common autoimmune disorders, such as multiple sclerosis or diabetes. In recent years, the trafficking of maternal cells to the offspring has been clearly demonstrated. This microchimerism represents the very first immunological event in fetal life. The number of persisting maternal cells has been associated with several autoimmune disorders such as systemic sclerosis, juvenile dermatomyositis or diabetes. Though, the precise role of the maternal cells in these disorders remains unclear. Based on recent experimental work in an animal model of juvenile diabetes, we will discuss the possibility of maternal cells modifying the response of the developing fetal immunity towards self.","PeriodicalId":89114,"journal":{"name":"Chimerism","volume":"2 1","pages":"71 - 77"},"PeriodicalIF":0.0,"publicationDate":"2011-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4161/chim.17589","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"70621233","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correlation between post transplant maternal microchimerism and tolerance across MHC barriers in mice.","authors":"Partha Dutta,&nbsp;William J Burlingham","doi":"10.4161/chim.2.3.18083","DOIUrl":"https://doi.org/10.4161/chim.2.3.18083","url":null,"abstract":"<p><strong>Unlabelled: </strong>Exposure to non-inherited maternal antigens (NIMA) during fetal and neonatal life can result in lifelong maternal microchimerism (MMc) and tolerance to NIMA(+) allografts. We have previously shown that 40-50% of BDF1 female x B6 male offspring have multi-organ and multi-lineage MMc, while 70% have evidence of acquired maternal class I antigen in circulating PBMC and splenocytes. These features correlated with the presence of NIMA(d)-specific CD4(+) Treg cells, while offspring lacking MMc also lacked NIMA-specific Tregs. Furthermore, after a DBA/2 heart transplant, NIMA(d)-specific CD4(+) Treg cells rapidly mobilize to the allograft where they produce IL10 and TGFβ, suppressing early acute rejection, while mice deficient in MMc and NIMA(d)-specific Treg reject, allowing IFNγ-producing T effector cells to predominate in the grafts. We hypothesized that maternal cells occupy key sites of alloantigen presentation after transplant, sustaining pre-existing host Treg amidst a rising tide of donor alloantigen released from the graft. Using quantitative PCR to detect GFP transgeneic maternal cells, we found that transplant tolerance was associated with elevated MMc levels in blood, heart & lung, but surprisingly, not in liver. Rejection was associated with significantly lower levels of MMc in CD11b(+) (p = 0.0001) and CD11c(+) (p = 0.045) splenocytes, but not with differences in T cell MMc. Furthermore, compared with low pre-transplant baseline rate of maternal antigen acquisition, long-term graft survival was associated with an increased mean % of cells in blood [0.5% pre vs. 5.0% post] and spleen that were dimly positive for H-2K(d), indicative of de novo cell-surface alloantigen acquisition from the DBA/2 donor heart allograft. In contrast, NIMA-exposed mice that rejected their DBA/2 graft showed a transient increase in H-2K(d-dim) cells in blood during rejection (day 9-12) but a complete absence of donor MHC acquisition 100 days after transplant. As was the case prior to transplant, antigen acquisition was largely confined to MHC class II+ professional APC.</p><p><strong>Conclusion: </strong>When a NIMA-expressing organ allograft is accepted, MMc persists, mainly distributed into the antigen-presenting cell compartment, where the bulk of graft-derived alloantigen for \"semi-direct\" presentation is also present.</p>","PeriodicalId":89114,"journal":{"name":"Chimerism","volume":"2 3","pages":"78-83"},"PeriodicalIF":0.0,"publicationDate":"2011-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3234359/pdf/chim0203_0078.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30320013","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correlation between post transplant maternal microchimerism and tolerance across MHC barriers in mice","authors":"Partha Dutta, W. Burlingham","doi":"10.4161/chim.18083","DOIUrl":"https://doi.org/10.4161/chim.18083","url":null,"abstract":"Exposure to non-inherited maternal antigens (NIMA) during fetal and neonatal life can result in lifelong maternal microchimerism (MMc) and tolerance to NIMA+ allografts. We have previously shown that 40-50% of BDF1 female x B6 male offspring have multi-organ and multi-lineage MMc, while 70% have evidence of acquired maternal class I antigen in circulating PBMC and splenocytes. These features correlated with the presence of NIMAd-specific CD4+ Treg cells, while offspring lacking MMc also lacked NIMA-specific Tregs. Furthermore, after a DBA/2 heart transplant, NIMAd-specific CD4+ Treg cells rapidly mobilize to the allograft where they produce IL10 and TGFβ, suppressing early acute rejection, while mice deficient in MMc and NIMAd-specific Treg reject, allowing IFNγ-producing T effector cells to predominate in the grafts. We hypothesized that maternal cells occupy key sites of alloantigen presentation after transplant, sustaining pre-existing host Treg amidst a rising tide of donor alloantigen released from the graft. Using quantitative PCR to detect GFP transgeneic maternal cells, we found that transplant tolerance was associated with elevated MMc levels in blood, heart & lung, but surprisingly, not in liver. Rejection was associated with significantly lower levels of MMc in CD11b+ (p=0.0001) and CD11c+ (p=0.045) splenocytes, but not with differences in T cell MMc. Furthermore, compared with low pre-transplant baseline rate of maternal antigen acquisition, long-term graft survival was associated with an increased mean % of cells in blood [0.5% pre vs. 5.0% post] and spleen that were dimly positive for H-2Kd, indicative of de novo cell-surface alloantigen acquisition from the DBA/2 donor heart allograft. In contrast, NIMA-exposed mice that rejected their DBA/2 graft showed a transient increase in H-2Kd-dim cells in blood during rejection (day 9-12) but a complete absence of donor MHC acquisition 100 days after transplant. As was the case prior to transplant, antigen acquisition was largely confined to MHC class II+ professional APC. Conclusion: When a NIMA-expressing organ allograft is accepted, MMc persists, mainly distributed into the antigen-presenting cell compartment, where the bulk of graft-derived alloantigen for \"semi-direct\" presentation is also present.","PeriodicalId":89114,"journal":{"name":"Chimerism","volume":"2 1","pages":"78 - 83"},"PeriodicalIF":0.0,"publicationDate":"2011-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4161/chim.18083","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"70621064","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pregnancy and the risk of autoimmune disease: An exploration.","authors":"Keelin O'Donoghue","doi":"10.4161/chim.2.3.17771","DOIUrl":"https://doi.org/10.4161/chim.2.3.17771","url":null,"abstract":"<p><p>Fetal microchimerism is the study of persisting fetal cells in the mother years after pregnancy and the purported implications for her health and longevity. Due to the association between pregnancy and autoimmune disease (AID), and the preponderance of these diseases in women, laboratory studies have for years attempted to link microchimeric fetal cells with the onset of AID after pregnancy. This new study gave us the opportunity to examine for the first time if this theory could be proven clinically in a large cohort of women. By examining whether different types of delivery affected the onset of AID, we also aimed to indirectly relate this finding to fetal microchimerism. The results did suggest an association between pregnancy and the risk of subsequent maternal AID, with increased risks noted after caesarean section (CS) and decreased risks after abortion. This is the first epidemiological study on the risk of AID following pregnancy. </p>","PeriodicalId":89114,"journal":{"name":"Chimerism","volume":"2 3","pages":"84-5"},"PeriodicalIF":0.0,"publicationDate":"2011-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4161/chim.2.3.17771","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30320014","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cadaveric bone marrow as potential source of hematopoietic stem cells for transplantation.","authors":"Jana Michalova,&nbsp;Filipp Savvulidi,&nbsp;Ludek Sefc,&nbsp;Katarina Forgacova,&nbsp;Emanuel Necas","doi":"10.4161/chim.2.3.17917","DOIUrl":"10.4161/chim.2.3.17917","url":null,"abstract":"<p><p>Every year, bone marrow transplantation saves many lives worldwide. Unfortunately, a suitable donor is not always available. Since organs are routinely harvested from cadaveric organ donors, we decided to assess such a possibility for bone marrow. We analyzed the functional properties and phenotypic markers of murine hematopoietic stem and progenitor cells (HSPC) from cadaveric bone marrow and during storage in vitro in a suspension. It was demonstrated that HSPC exposed to a warm or cold ischemia in intact femur did not lose their phenotype and maintained their repopulating ability for two to twelve hours depending on the temperature. Additionally, fresh bone marrow remained fully viable in cell suspension for two days or four days at 37°C or 4°C, respectively. Based on these findings, cadaveric bone marrow could be considered as an alternative source of hematopoietic stem cells for transplantation. </p>","PeriodicalId":89114,"journal":{"name":"Chimerism","volume":"2 3","pages":"86-7"},"PeriodicalIF":0.0,"publicationDate":"2011-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3234361/pdf/chim0203_0086.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30320015","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Can maternal microchimeric cells influence the fetal response toward self antigens?","authors":"Lucie Leveque,&nbsp;Kiarash Khosrotehrani","doi":"10.4161/chim.2.3.17589","DOIUrl":"https://doi.org/10.4161/chim.2.3.17589","url":null,"abstract":"<p><p>The origins of autoimmunity are still elusive despite significant advances in immunology. There is cumulative evidence that, beyond simple genetics, the maternal environment plays a critical role in the development of common autoimmune disorders, such as multiple sclerosis or diabetes. In recent years, the trafficking of maternal cells to the offspring has been clearly demonstrated. This microchimerism represents the very first immunological event in fetal life. The number of persisting maternal cells has been associated with several autoimmune disorders such as systemic sclerosis, juvenile dermatomyositis and diabetes. The precise role of the maternal cells in these disorders remains unclear. Based on recent experimental work in an animal model of juvenile diabetes, we will discuss the possibility of maternal cells modifying the response of the developing fetal immunity towards self. </p>","PeriodicalId":89114,"journal":{"name":"Chimerism","volume":"2 3","pages":"71-7"},"PeriodicalIF":0.0,"publicationDate":"2011-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3234358/pdf/chim0203_0071.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30320012","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cadaveric bone marrow as potential source of hematopoietic stem cells for transplantation","authors":"Jana Míchalová, F. Savvulidi, L. Šefc, K. Forgáčová, E. Nečas","doi":"10.4161/chim.17917","DOIUrl":"https://doi.org/10.4161/chim.17917","url":null,"abstract":"Every year, bone marrow transplantation saves many lives worldwide. Unfortunately, a suitable donor is not always available. Since organs are routinely harvested from cadaveric organ donors, we decided to assess such a possibility for bone marrow. We analyzed the functional properties and phenotypic markers of murine hematopoietic stem and progenitor cells (HSPC) from cadaveric bone marrow and during storage in vitro in a suspension. It was demonstrated that HSPC exposed to a warm or cold ischemia in intact femur did not lose their phenotype and maintained their repopulating ability for 2 to 12 hours depending on the temperature. Additionally, fresh bone marrow remained fully viable in cell suspension for 2 days or 4 days at 37°C or 4°C, respectively. Based on these findings, cadaveric bone marrow could be considered as an alternative source of hematopoietic stem cells for transplantation.","PeriodicalId":89114,"journal":{"name":"Chimerism","volume":"2 1","pages":"1281 - 86 - 87"},"PeriodicalIF":0.0,"publicationDate":"2011-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4161/chim.17917","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"70620991","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Verification of the genomic identity of candidate microchimeric cells.","authors":"Peter Sedlmayr,&nbsp;Thomas Kroneis","doi":"10.4161/chim.2.3.17741","DOIUrl":"https://doi.org/10.4161/chim.2.3.17741","url":null,"abstract":"<p><p>Microchimerism has been studied in the context of a variety of diseases which include autoimmune diseases (such as systemic sclerosis, rheumatoid arthritis, systemic lupus erythematosus and autoimmune thyroid diseases), cancer (e.g., of the cervix, thyroid gland, lung, breast), tissue repair, transplantation and transfusion. It may become relevant in the context of cell-based non-invasive prenatal diagnosis. But how to safely identify individual microchimeric cells? This is a nontrivial question, for which a solution has recently been suggested. </p>","PeriodicalId":89114,"journal":{"name":"Chimerism","volume":"2 3","pages":"63-4"},"PeriodicalIF":0.0,"publicationDate":"2011-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3234356/pdf/chim0203_0063.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30320010","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The role of pDC, recipient Treg, and donor Treg in HSC engraftment","authors":"P. Cárdenas, Yiming Huang, S. Ildstad","doi":"10.4161/chim.17588","DOIUrl":"https://doi.org/10.4161/chim.17588","url":null,"abstract":"Hematopoietic stem cell (HSC) transplantation (HSCT) has been utilized for treatment of many hematologic malignancies, genetic and metabolic disorders, and hemoglobinopathies such as sickle cell disease and thalassemia. It also induces donor-specific tolerance to organ and tissue transplants. The widespread success of HSCT is hampered by the toxicities of immunosuppression and development of graft-versus-host disease (GVHD). The mechanism of induction of transplantation tolerance (reciprocal donor/host) is still an elusive challenge in allogeneic HSCT. An understanding of the mechanisms for induction of tolerance and the critical cells involved in this process has resulted in novel cell-based therapies poised to be translated to clinical application. The focus of this review is those cells of interest. Bone marrow-derived plasmacytoid dendritic cells induce naïve T cells to differentiate to become antigen-specific regulatory T cells (Treg), creating a milieu for the induction of transplantation tolerance. Recently, CD8+/TCR- facilitating cells (FC), a novel cell population in mouse bone marrow, have been shown to potently enhance engraftment of allogeneic HSC without causing GVHD. The predominant subpopulation of FC resembles plasmacytoid precursor dendritic cells. FC induce antigen-specific Treg in vivo. Notably, FC address one major concern that has prevented the implementation of Treg cell therapy in the clinic: to expand Treg and have them remain tolerogenic in vivo. FC are novel in that they induce an antigen-specific regulatory milieu in vivo. The discovery of FC has opened new alternatives to expanded criteria in bone marrow transplantation that were previously restricted to human leukocyte antigen-matched recipients. The focus of this review is to cover what is currently known about the mechanism of FC action in inducing tolerance and preventing GVHD and host-versus-graft reactivity.","PeriodicalId":89114,"journal":{"name":"Chimerism","volume":"12 1","pages":"65 - 70"},"PeriodicalIF":0.0,"publicationDate":"2011-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4161/chim.17588","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"70620973","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}