Chimerism最新文献

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Tolerance induction after organ transplantation, "delayed tolerance," via the mixed chimerism approach: planting flowers in a battle field. 器官移植后的耐受性诱导,“延迟耐受性”,通过混合嵌合的方式:在战场上种花。
Chimerism Pub Date : 2012-01-01 DOI: 10.4161/chim.20096
Yohei Yamada, Gilles Benichou, A Benedict Cosimi, Tatsuo Kawai
{"title":"Tolerance induction after organ transplantation, \"delayed tolerance,\" via the mixed chimerism approach: planting flowers in a battle field.","authors":"Yohei Yamada, Gilles Benichou, A Benedict Cosimi, Tatsuo Kawai","doi":"10.4161/chim.20096","DOIUrl":"https://doi.org/10.4161/chim.20096","url":null,"abstract":"We have previously reported that peri-transplant conditioning leads to successful induction of renal allograft tolerance via the mixed chimerism approach in nonhuman primates (NHP) and humans. However, this strategy requires treatments beginning six days prior to transplantation, which limits its relevance only to living donor transplant recipients. To extend the clinical applicability of this approach, we developed a novel regimen “delayed tolerance,” with which the recipient initially undergoes organ transplantation with conventional immunosuppression, followed by conditioning and donor bone marrow transplantation (DBMT) at a later date. This approach might be likened to “planting flowers in a battle field.” That is, the recipient’s immunologic environment after organ transplantation is like a battlefield filled with hostile innate and adaptive immune-responses directed against donor antigeneic specificities. Implanting fragile donor hematopoietic progenitors into this environment and encouraging them to bloom in this vicious field requires special treatments. In our NHP studies recently published in The American Journal of Transplantation, we showed that such “delayed tolerance,” in fact, can be induced in NHP through the mixed chimerism approach, if specific modifications to overcome/avoid donor-specific memory T cell responses are provided. These modifications include adequate depletion of CD8 memory T cells and timing of donor bone marrow administration to minimize levels of pro-inflammatory cytokines. This article addendum will provide a short summary of the original paper with our additional insights and interpretations.","PeriodicalId":89114,"journal":{"name":"Chimerism","volume":"3 1","pages":"24-8"},"PeriodicalIF":0.0,"publicationDate":"2012-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4161/chim.20096","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30684179","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}
引用次数: 13
Fetal-maternal interface: a chronicle of allogeneic coexistence. 胎母界面:异基因共存的编年史。
Chimerism Pub Date : 2012-01-01 DOI: 10.4161/chim.19439
Josep-Maria Pujal, Santiago Roura, Ana M Muñoz-Marmol, Jose-Luis Mate, Antoni Bayes-Genis
{"title":"Fetal-maternal interface: a chronicle of allogeneic coexistence.","authors":"Josep-Maria Pujal,&nbsp;Santiago Roura,&nbsp;Ana M Muñoz-Marmol,&nbsp;Jose-Luis Mate,&nbsp;Antoni Bayes-Genis","doi":"10.4161/chim.19439","DOIUrl":"https://doi.org/10.4161/chim.19439","url":null,"abstract":"<p><p>The existence of allogeneic cells within an individual has been demonstrated in multiple fields such as hematopoietic stem cell or solid organ transplantation, non-depleted blood transfusions and the most common form which is bidirectional maternal-fetal cell trafficking, whereby cells from the fetus pass through the placental barrier. In order to graphically illustrate this early natural phenomenon that initiates the journey of a child's cells within the mother's blood and other tissues, we used a new procedure in microscopy imaging generating Large Scale Panoramic Pictures (LSPP). This technique can also be extended to explore a broad diversity of experimental models.</p>","PeriodicalId":89114,"journal":{"name":"Chimerism","volume":"3 1","pages":"18-20"},"PeriodicalIF":0.0,"publicationDate":"2012-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4161/chim.19439","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30684177","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}
引用次数: 5
Immigration control in the vertebrate body with special reference to chimerism. 脊椎动物体内的移入控制,特别涉及嵌合。
Chimerism Pub Date : 2012-01-01 DOI: 10.4161/chim.20113
Anthony J S Davies
{"title":"Immigration control in the vertebrate body with special reference to chimerism.","authors":"Anthony J S Davies","doi":"10.4161/chim.20113","DOIUrl":"https://doi.org/10.4161/chim.20113","url":null,"abstract":"<p><p>The phenomenon of chimerism is reviewed against an understanding of adaptive immunity in vertebrates. It is shown that chimerism can be regarded as a ubiquitous condition and this suggests that monophylesis has played little part in evolution. It is suggested that the adaptive immune response has a special role in facilitating the development of chimerism and that the consensus view of adaptive immunity as a rejection mechanism should be revised.</p>","PeriodicalId":89114,"journal":{"name":"Chimerism","volume":"3 1","pages":"1-8"},"PeriodicalIF":0.0,"publicationDate":"2012-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4161/chim.20113","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30684175","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}
引用次数: 10
Utility of saliva and hair follicles in donor selection for hematopoietic stem cell transplantation and chimerism monitoring. 唾液和毛囊在造血干细胞移植供体选择和嵌合监测中的应用。
Chimerism Pub Date : 2012-01-01 DOI: 10.4161/chim.19395
Gurvinder Kaur, Neeraj Kumar, Ramya Nandakumar, Chowphi C Rapthap, Gaurav Sharma, Shekhar Neolia, Heena Kumra, Prateek Mahalwar, Abhinav Garg, Sunil Kumar, Jasmeet Kaur, Mrinali Hakim, Lalit Kumar, Narinder K Mehra
{"title":"Utility of saliva and hair follicles in donor selection for hematopoietic stem cell transplantation and chimerism monitoring.","authors":"Gurvinder Kaur,&nbsp;Neeraj Kumar,&nbsp;Ramya Nandakumar,&nbsp;Chowphi C Rapthap,&nbsp;Gaurav Sharma,&nbsp;Shekhar Neolia,&nbsp;Heena Kumra,&nbsp;Prateek Mahalwar,&nbsp;Abhinav Garg,&nbsp;Sunil Kumar,&nbsp;Jasmeet Kaur,&nbsp;Mrinali Hakim,&nbsp;Lalit Kumar,&nbsp;Narinder K Mehra","doi":"10.4161/chim.19395","DOIUrl":"https://doi.org/10.4161/chim.19395","url":null,"abstract":"<p><p>Selection of an HLA identical donor is a critical pre-requisite for successful hematopoietic stem cell transplantation (HSCT). Most transplant centers utilize blood as the most common source of DNA for HLA testing. However, obtaining blood through phlebotomy is often challenging in patients with conditions like severe leucopenia or hemophilia, pediatric and elderly patients. We have used a simple in-house protocol and shown that HLA genotypes obtained on DNA extracted from saliva or hair are concordant with blood and hence can be used for selection of donors for HSCT or organ transplantation. Similarly, for post-HSCT chimerism monitoring, non-availability of pre-transplant DNA samples poses a major limitation of reference STR fingerprints. This study shows that DNA obtained post-HSCT from hair follicles can be used to generate pre-transplant patient specific fingerprints while the STR profiles obtained in saliva samples cannot as these display a mixed state of chimerism.</p>","PeriodicalId":89114,"journal":{"name":"Chimerism","volume":"3 1","pages":"9-17"},"PeriodicalIF":0.0,"publicationDate":"2012-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4161/chim.19395","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30684176","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}
引用次数: 9
Donor-derived peripheral mononuclear cell DNA is associated with stable kidney allograft function: a randomized controlled trial. 供体来源的外周单核细胞DNA与稳定的同种异体肾移植功能相关:一项随机对照试验。
Chimerism Pub Date : 2011-10-01 DOI: 10.4161/chim.2.4.19095
Ghasem Solgi, Joannis Mytilineos, Vijayakrishna Gadi, Biswajit Paul, Gholamreza Pourmand, Abdolrasoul Mehrsai, Behrouz Nikbin, Ali Akbar Amirzargar
{"title":"Donor-derived peripheral mononuclear cell DNA is associated with stable kidney allograft function: a randomized controlled trial.","authors":"Ghasem Solgi,&nbsp;Joannis Mytilineos,&nbsp;Vijayakrishna Gadi,&nbsp;Biswajit Paul,&nbsp;Gholamreza Pourmand,&nbsp;Abdolrasoul Mehrsai,&nbsp;Behrouz Nikbin,&nbsp;Ali Akbar Amirzargar","doi":"10.4161/chim.2.4.19095","DOIUrl":"https://doi.org/10.4161/chim.2.4.19095","url":null,"abstract":"A large body of literature has documented an inconsistent relationship of peripheral donor cell chimerism with alloimmune tolerance following kidney transplantation. We revisit this association with assays capable of quantifying cellular microchimerism with 150–1500-fold greater sensitivity than previously utilized allo-antibody based flow cytometric approaches. Forty renal transplant patients, 20 with concurrent donor bone marrow infusion (DBMI) and 20 control participants without infusion were prospectively monitored for peripheral blood microchimerism using donor polymorphism-specific quantitative real-time PCR. Thirty-eight patients were evaluated for microchimerism, 19 in each group. The frequency of testing positive for (95% vs. 58%, p = 0.02) and mean concentrations of microchimerism (115 ± 66 vs. 13 ± 3 donor genomes/million recipient genomes, p = 0.007), respectively, were higher in infused patients compared with controls. Thirty-one patients maintained stable graft function; 17 in the DBMI group vs. 14 in controls. Patients with stable graft function in the DBMI group compared with control patients harbored microchimerism more frequently (94 vs. 50%, p = 0.01) and at higher concentrations (123 ± 67 vs. 11 ± 4, p = 0.007), respectively. Significant correlation between dose of infused cells and microchimerism levels was found post-transplant (p = 0.01). Using very sensitive assays, our findings demonstrate associations between the presence and quantity of microchimerism with stable graft function in infused patients.","PeriodicalId":89114,"journal":{"name":"Chimerism","volume":"2 4","pages":"102-10"},"PeriodicalIF":0.0,"publicationDate":"2011-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4161/chim.2.4.19095","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30579843","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}
引用次数: 6
Th2 alloimmunity counteracts Th17-type response in the neonatal establishment of lymphoid chimerism. Th2同种免疫在新生儿淋巴嵌合的建立中抵消th17型反应。
Chimerism Pub Date : 2011-10-01 DOI: 10.4161/chim.2.4.19162
Isabelle Debock, Véronique Flamand
{"title":"Th2 alloimmunity counteracts Th17-type response in the neonatal establishment of lymphoid chimerism.","authors":"Isabelle Debock,&nbsp;Véronique Flamand","doi":"10.4161/chim.2.4.19162","DOIUrl":"https://doi.org/10.4161/chim.2.4.19162","url":null,"abstract":"<p><p>The neonatal period of life is described as particularly susceptible to develop tolerance. This status of neonatal tolerance has been studied for decades since the discovery that semiallogeneic spleen cells inoculated at birth can induce donor-type graft acceptance. The host neonatal T‑cell compartment that may account for this propensity to develop tolerance is mostly characterized by a Th2-type polarized response and a default in the cytotoxic T lymphocyte (CTL) functions that allow the establishment of lymphoid chimerism and promote donor-type graft survival. We highlighted a new role of alloreactive Th17 cells as a critical barrier to neonatal tolerance that prevents this lymphoid chimerism and further demonstrated that the Th2 immune deviation is essential to control this Th17-type response. We discuss here the potential impact of breaking the tolerizing effects of exposure of the developing offspring to alloantigens in the induction of Th17-type immunity.</p>","PeriodicalId":89114,"journal":{"name":"Chimerism","volume":"2 4","pages":"117-9"},"PeriodicalIF":0.0,"publicationDate":"2011-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4161/chim.2.4.19162","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30579842","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}
引用次数: 2
Host stem cells repopulate liver allografts: reverse chimerism. 宿主干细胞重新填充同种异体肝脏移植物:反向嵌合。
Chimerism Pub Date : 2011-10-01 DOI: 10.4161/chim.2.4.19177
Zhaoli Sun, George Melville Williams
{"title":"Host stem cells repopulate liver allografts: reverse chimerism.","authors":"Zhaoli Sun,&nbsp;George Melville Williams","doi":"10.4161/chim.2.4.19177","DOIUrl":"https://doi.org/10.4161/chim.2.4.19177","url":null,"abstract":"<p><p>Liver transplant has become life-saving therapy for thousands of patients with end stage liver disease in the United States, but chronic rejection and the toxicities of immunosuppression remain significant obstacles to the further expansion of this modality and \"transplant tolerance\" remains a central goal in the field. So we and others are looking for alternative post-transplant strategies. We set out to 'engineer' repopulation after transplantation in a strain combination [dark agouti (DA) to Lewis green fluorescent protein+ (LEW GFP+)] which rejects liver grafts strongly, a model that more closely resembles the situation in humans. Our central finding is purposeful manipulation of the immune response with low dose immunosuppression and liberation of stem cells for a very short period after transplantation results in long-term transplant acceptance by two mechanisms: transforming the liver (donor) to self (host) phenotype, and auto-suppression of the specific allograft response.</p>","PeriodicalId":89114,"journal":{"name":"Chimerism","volume":"2 4","pages":"120-2"},"PeriodicalIF":0.0,"publicationDate":"2011-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4161/chim.2.4.19177","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30579844","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}
引用次数: 5
HLA-targeted cell sorting of microchimeric cells opens the way to phenotypical and functional characterization. hla靶向细胞分选为嵌合细胞的表型和功能表征开辟了道路。
Chimerism Pub Date : 2011-10-01 DOI: 10.4161/chim.2.4.19133
Michael Eikmans, Frans H J Claas
{"title":"HLA-targeted cell sorting of microchimeric cells opens the way to phenotypical and functional characterization.","authors":"Michael Eikmans,&nbsp;Frans H J Claas","doi":"10.4161/chim.2.4.19133","DOIUrl":"https://doi.org/10.4161/chim.2.4.19133","url":null,"abstract":"<p><p>Microchimerism refers to the presence of less than 1% of non-host cells in a person. Our group developed a reliable method for separating viable microchimeric cells from the host environment. Optimal separation of microchimeric cells at proportions as low as 0.01% could be established with two monoclonal antibodies directed against different HLA antigens, one targeting the microchimeric cells and the other the host cells. Purity of separated cell populations was validated by HLA-allele-specific and Y-chromosome directed real-time qPCR assays. The methodology was used successfully to separate microchimeric maternal cells from child umbilical cord mononuclear cells after pregnancy. Cell sorting with HLA monoclonal antibodies targeting allelic differences enables reliable microchimeric cell detection and separation in blood specimens. With this approach, maximal enrichment of potentially viable microchimeric cells from a background cell population is reached, which opens the way to phenotypical and functional characterization of microchimeric cells.</p>","PeriodicalId":89114,"journal":{"name":"Chimerism","volume":"2 4","pages":"114-6"},"PeriodicalIF":0.0,"publicationDate":"2011-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4161/chim.2.4.19133","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30579841","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}
引用次数: 3
Mixed chimerism and split tolerance: mechanisms and clinical correlations. 混合嵌合和分裂耐受:机制和临床相关性。
Chimerism Pub Date : 2011-10-01 DOI: 10.4161/chim.2.4.19017
David P Al-Adra, Colin C Anderson
{"title":"Mixed chimerism and split tolerance: mechanisms and clinical correlations.","authors":"David P Al-Adra,&nbsp;Colin C Anderson","doi":"10.4161/chim.2.4.19017","DOIUrl":"https://doi.org/10.4161/chim.2.4.19017","url":null,"abstract":"<p><p>Establishing hematopoietic mixed chimerism can lead to donor-specific tolerance to transplanted organs and may eliminate the need for long-term immunosuppressive therapy, while also preventing chronic rejection. In this review, we discuss central and peripheral mechanisms of chimerism induced tolerance. However, even in the long-lasting presence of a donor organ or donor hematopoietic cells, some allogeneic tissues from the same donor can be rejected; a phenomenon known as split tolerance. With the current goal of creating mixed chimeras using clinically feasible amounts of donor bone marrow and with minimal conditioning, split tolerance may become more prevalent and its mechanisms need to be explored. Some predisposing factors that may increase the likelihood of split tolerance are immunogenicity of the graft, certain donor-recipient combinations, prior sensitization, location and type of graft and minimal conditioning chimerism induction protocols. Additionally, split tolerance may occur due to a differential susceptibility of various types of tissues to rejection. The mechanisms involved in a tissue's differential susceptibility to rejection include the presence of polymorphic tissue-specific antigens and variable sensitivity to indirect pathway effector mechanisms. Finally, we review the clinical attempts at allograft tolerance through the induction of chimerism; studies that are revealing the complex relationship between chimerism and tolerance. This relationship often displays split tolerance, and further research into its mechanisms is warranted.</p>","PeriodicalId":89114,"journal":{"name":"Chimerism","volume":"2 4","pages":"89-101"},"PeriodicalIF":0.0,"publicationDate":"2011-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4161/chim.2.4.19017","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30578310","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}
引用次数: 25
Layers of regulation in induction of mixed chimerism by anti-CD40L. 抗 CD40L 诱导混合嵌合体过程中的多层调节。
Chimerism Pub Date : 2011-10-01 DOI: 10.4161/chim.2.4.19053
Carrie L Lucas, Megan Sykes
{"title":"Layers of regulation in induction of mixed chimerism by anti-CD40L.","authors":"Carrie L Lucas, Megan Sykes","doi":"10.4161/chim.2.4.19053","DOIUrl":"10.4161/chim.2.4.19053","url":null,"abstract":"<p><p>The pathways regulating immunological tolerance are complex and overlapping. Here, we comment on our findings that the PD-1, CTLA-4, LAG-3 and TGFβ inhibitory molecules are all involved in mediating peripheral CD8 T‑cell tolerance induced by anti-CD40L and allogeneic bone marrow transplantation in mice. These observations suggest the possibility of targeted manipulation of these pathways for induction of mixed hematopoietic chimerism for donor-specific transplantation tolerance.</p>","PeriodicalId":89114,"journal":{"name":"Chimerism","volume":"2 4","pages":"111-3"},"PeriodicalIF":0.0,"publicationDate":"2011-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3321881/pdf/chim-2-111.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30578311","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}
引用次数: 0
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