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[PMID]:28888053
[Au] Autor:Guo H; Zhao N; Gao H; He X
[Ad] Endereço:Department of General Surgery, Tianjin Medical University General Hospital, Tianjin, China.
[Ti] Título:Mesenchymal Stem Cells Overexpressing Interleukin-35 Propagate Immunosuppressive Effects in Mice.
[So] Source:Scand J Immunol;86(5):389-395, 2017 Nov.
[Is] ISSN:1365-3083
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:To explore generation of interleukin (IL)-35-expressing mouse adipocyte-derived mesenchymal stem cells (Ad-MSCs) using lentiviral vector and their potential immunosuppressive effects in mice. Ad-MSCs were isolated and cultured in vitro and transfected with a lentivirus vector for overexpression of the therapeutic murine IL-35 gene. IL-35 expression in transfected MSCs (IL-35-MSCs) was quantified by enzyme-linked immunosorbent assay (ELISA). The lymphocytes subsets after one-way mixed lymphocyte culture and in vivo intravenous transplantation were analysed by flow cytometry to evaluate the immunosuppressive effects of IL-35-MSCs. ELISA was performed to examine IL-10, IL-17A and IL-35 expression in lymphocyte culture. Mouse Ad-MSCs were isolated and cultured. IL-35 was expressed in the MSC supernatant and serum after IL-35 transduction into Ad-MSCs by lentiviral vector transfection in vitro and in vivo. The percentage of CD4 CD25 T regulatory (Treg) cells in mice treated with IL-35-MSCs significantly increased. IL-35-MSCs upregulated the CD4 CD25 Treg cells in the allogeneic mixed lymphocyte reaction system, and lowered the percentage of CD4 T cells compared with the other two control groups (P < 0.01). IL-17A expression significantly decreased and IL-10 expression significantly increased in IL-35-MSCs and MSCs when compared by ELISA to the control groups (P < 0.01). IL-35-transduced Ad-MSCs in vivo can enhance proliferation of CD4 CD25 Treg cells and suppress the function of effector T cells such as T helper (Th) 1, Th2 and Th17 cells and may reduce the development of allograft rejection. Our data suggest that transduced Ad-MSCs overexpressing IL-35 may provide a useful approach for basic research on cell-based immunotolerance therapy for inducing transplantation tolerance.
[Mh] Termos MeSH primário: Tolerância Imunológica
Interleucinas/metabolismo
Células Mesenquimais Estromais/imunologia
[Mh] Termos MeSH secundário: Adipócitos/citologia
Adipócitos/imunologia
Animais
Células Cultivadas
Interleucinas/genética
Teste de Cultura Mista de Linfócitos
Masculino
Transplante de Células-Tronco Mesenquimais
Células Mesenquimais Estromais/citologia
Camundongos
Camundongos Endogâmicos BALB C
Camundongos Endogâmicos C57BL
Proteínas Recombinantes/genética
Proteínas Recombinantes/metabolismo
Linfócitos T Auxiliares-Indutores/imunologia
Linfócitos T Reguladores/imunologia
Transfecção
Tolerância ao Transplante
Regulação para Cima
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Interleukins); 0 (Recombinant Proteins); 0 (interleukin-35, mouse)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171023
[Lr] Data última revisão:
171023
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170910
[St] Status:MEDLINE
[do] DOI:10.1111/sji.12613


  2 / 2188 MEDLINE  
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[PMID]:28848066
[Au] Autor:Ding Q; Mohib K; Kuchroo VK; Rothstein DM
[Ad] Endereço:Thomas E. Starzl Transplantation Institute, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261.
[Ti] Título:TIM-4 Identifies IFN-γ-Expressing Proinflammatory B Effector 1 Cells That Promote Tumor and Allograft Rejection.
[So] Source:J Immunol;199(7):2585-2595, 2017 Oct 01.
[Is] ISSN:1550-6606
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:B cells give rise to polarized subsets, including B effector 1 (Be1) cells and regulatory B cells, which can promote or inhibit immune responses through expression of IFN-γ and IL-10, respectively. Such subsets likely explain why B cell depletion can either ameliorate or exacerbate inflammatory diseases; however, these cells remain poorly understood because of the absence of specific markers. Although T cell Ig and mucin domain-containing molecule (TIM)-1 broadly identifies IL-10 regulatory B cells, no similar markers for Be1 cells have been described. We now show that TIM-4 is expressed by a subset of B cells distinct from those expressing TIM-1. Although TIM-1 B cells are enriched for IL-10, TIM-4 B cells are enriched for IFN-γ. TIM-1 B cells enhanced the growth of B16-F10 melanoma. In contrast, TIM-4 B cells decreased B16-F10 metastasis and s.c. tumor growth, and this was IFN-γ dependent. TIM-1 B cells prolonged islet allograft survival in B-deficient mice, whereas TIM-4 B cells accelerated rejection in an IFN-γ-dependent manner. Moreover, TIM-4 B cells promoted proinflammatory Th differentiation in vivo, increasing IFN-γ while decreasing IL-4, IL-10, and Foxp3 expression by CD4 T cells-effects that are opposite from those of TIM-1 B cells. Importantly, a monoclonal anti-TIM-4 Ab promoted allograft tolerance, and this was dependent on B cell expression of TIM-4. Anti-TIM-4 downregulated T-bet and IFN-γ expression by TIM-4 B cells and indirectly increased IL-10 expression by TIM-1 B cells. Thus, TIM-4 B cells are enriched for IFN-γ-producing proinflammatory Be1 cells that enhance immune responsiveness and can be specifically targeted with anti-TIM-4.
[Mh] Termos MeSH primário: Aloenxertos/imunologia
Subpopulações de Linfócitos B/imunologia
Rejeição de Enxerto
Interferon gama/biossíntese
Melanoma Experimental/imunologia
Proteínas de Membrana/imunologia
Tolerância ao Transplante
[Mh] Termos MeSH secundário: Animais
Anticorpos Monoclonais/administração & dosagem
Diferenciação Celular
Fatores de Transcrição Forkhead/genética
Fatores de Transcrição Forkhead/metabolismo
Interleucina-10/genética
Interleucina-10/imunologia
Interleucina-4/imunologia
Ativação Linfocitária
Melanoma Experimental/patologia
Proteínas de Membrana/genética
Proteínas de Membrana/metabolismo
Camundongos
Metástase Neoplásica
Células Th1/fisiologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antibodies, Monoclonal); 0 (Forkhead Transcription Factors); 0 (Foxp3 protein, mouse); 0 (Membrane Proteins); 0 (TIM-4 protein, mouse); 130068-27-8 (Interleukin-10); 207137-56-2 (Interleukin-4); 82115-62-6 (Interferon-gamma)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:170830
[St] Status:MEDLINE
[do] DOI:10.4049/jimmunol.1602107


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[PMID]:28604446
[Au] Autor:Young JS; McIntosh C; Alegre ML; Chong AS
[Ad] Endereço:1 Section of Transplantation, Department of Surgery, The University of Chicago, Chicago, IL. 2 Section of Rheumatology, Department of Medicine, The University of Chicago, Chicago, IL.
[Ti] Título:Evolving Approaches in the Identification of Allograft-Reactive T and B Cells in Mice and Humans.
[So] Source:Transplantation;101(11):2671-2681, 2017 Nov.
[Is] ISSN:1534-6080
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Whether a transplanted allograft is stably accepted, rejected, or achieves immunological tolerance is dependent on the frequency and function of alloreactive lymphocytes, making the identification and analysis of alloreactive T and B cells in transplant recipients critical for understanding mechanisms, and the prediction of allograft outcome. In animal models, tracking the fate of graft-reactive T and B cells allows investigators to uncover their biology and develop new therapeutic strategies to protect the graft. In the clinic, identification and quantification of graft-reactive T and B cells allows for the early diagnosis of immune reactivity and therapeutic intervention to prevent graft loss. In addition to rejection, probing of T and B cell fate in vivo provides insights into the underlying mechanisms of alloimmunity or tolerance that may lead to biomarkers predicting graft fate. In this review, we discuss existing and developing approaches to track and analyze alloreactive T and B cells in mice and humans and provide examples of discoveries made utilizing these techniques. These approaches include mixed lymphocyte reactions, trans-vivo delayed-type hypersensitivity, enzyme-linked immunospot assays, the use of antigen receptor transgenic lymphocytes, and utilization of peptide-major histocompatibility multimers, along with imaging techniques for static multiparameter analysis or dynamic in vivo tracking. Such approaches have already refined our understanding of the alloimmune response and are pointing to new ways to improve allograft outcomes in the clinic.
[Mh] Termos MeSH primário: Linfócitos B/imunologia
Rejeição de Enxerto/prevenção & controle
Sobrevivência de Enxerto
Técnicas Imunológicas
Ativação Linfocitária
Transplante de Órgãos
Linfócitos T/imunologia
Tolerância ao Transplante
[Mh] Termos MeSH secundário: Aloenxertos
Animais
Linfócitos B/efeitos dos fármacos
Linfócitos B/metabolismo
Rejeição de Enxerto/sangue
Rejeição de Enxerto/imunologia
Sobrevivência de Enxerto/efeitos dos fármacos
Histocompatibilidade
Seres Humanos
Imunossupressores/uso terapêutico
Isoanticorpos/sangue
Ativação Linfocitária/efeitos dos fármacos
Camundongos
Modelos Animais
Transplante de Órgãos/efeitos adversos
Plasmócitos/imunologia
Fatores de Risco
Linfócitos T/efeitos dos fármacos
Linfócitos T/metabolismo
Tolerância ao Transplante/efeitos dos fármacos
Resultado do Tratamento
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Immunosuppressive Agents); 0 (Isoantibodies)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171106
[Lr] Data última revisão:
171106
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170613
[St] Status:MEDLINE
[do] DOI:10.1097/TP.0000000000001847


  4 / 2188 MEDLINE  
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[PMID]:28574903
[Au] Autor:Chhabra AY; Leventhal J; Merchak AR; Ildstad S
[Ad] Endereço:1 Institute for Cellular Therapeutics, University of Louisville, Louisville, KY. 2 Comprehensive Transplant Center, Northwestern Memorial Hospital, Chicago, IL.
[Ti] Título:HSCT-Based Approaches for Tolerance Induction in Renal Transplant.
[So] Source:Transplantation;101(11):2682-2690, 2017 Nov.
[Is] ISSN:1534-6080
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Renal transplantation has become the preferred treatment for end stage kidney failure. Although short-term graft survival has significantly improved as advances in immunosuppression have occurred, long-term patient and graft survival have not. Approximately only 50% of renal transplant recipients are alive at 10 years due to the toxicities of immunosuppression and alloimmunity. Emerging research on cell-based therapies is opening a new door for patients to receive the organs they need without sacrificing quality of life and longevity because of drug-based immunosuppression. Research has focused on inducing tolerance, a state in which the body accepts the transplant and graft function is stable. Cell-based therapies to facilitate chimerism and achieve tolerance in major histocompatibility disparate recipients have been developed in mouse, swine, canine, and nonhuman primate models. These findings are now being translated into the clinic in several trials currently underway. Protocols that use a combination of traditional therapeutic agents paired with cell populations including hematopoietic stem cells, regulatory T cells, and facilitating cells are being conducted with the objective to harness the donor immune system to protect the transplanted tissue. The benefits and feasibility of the clinical application of cell-based therapy has been demonstrated, and promising results have been achieved. Here we discuss the preclinical work that has led to the clinical application of the various approaches and a summary of the most current clinical data from groups throughout the world.
[Mh] Termos MeSH primário: Rejeição de Enxerto/prevenção & controle
Sobrevivência de Enxerto
Transplante de Células-Tronco Hematopoéticas
Transplante de Rim
Tolerância ao Transplante
[Mh] Termos MeSH secundário: Animais
Rejeição de Enxerto/imunologia
Transplante de Células-Tronco Hematopoéticas/efeitos adversos
Histocompatibilidade
Seres Humanos
Isoanticorpos/imunologia
Transplante de Rim/efeitos adversos
Modelos Animais
Especificidade da Espécie
Fatores de Tempo
Pesquisa Médica Translacional
Quimeras de Transplante/imunologia
Resultado do Tratamento
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Isoantibodies)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171106
[Lr] Data última revisão:
171106
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170603
[St] Status:MEDLINE
[do] DOI:10.1097/TP.0000000000001837


  5 / 2188 MEDLINE  
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[PMID]:28518214
[Au] Autor:Behnam Sani K; Sawitzki B
[Ad] Endereço:Institute of Medical Immunology, Charité Universitaetsmedizin Berlin, Berlin, Germany.
[Ti] Título:Immune monitoring as prerequisite for transplantation tolerance trials.
[So] Source:Clin Exp Immunol;189(2):158-170, 2017 Aug.
[Is] ISSN:1365-2249
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Ever since its first application in clinical medicine, scientists have been urged to induce tolerance towards foreign allogeneic transplants and thus avoid rejection by the recipient's immune system. This would circumvent chronic use of immunosuppressive drugs (IS) and thus avoid development of IS-induced side effects, which are contributing to the still unsatisfactory long-term graft and patient survival after solid organ transplantation. Although manifold strategies of tolerance induction have been described in preclinical models, only three therapeutic approaches have been utilized successfully in a still small number of patients. These approaches are based on (i) IS withdrawal in spontaneous operational tolerant (SOT) patients, (ii) induction of a mixed chimerism and (iii) adoptive transfer of regulatory cells. Results of clinical trials utilizing these approaches show that tolerance induction does not work in all patients. Thus, there is a need for reliable biomarkers, which can be used for patient selection and post-therapeutic immune monitoring of safety, success and failure. In this review, we summarize recent achievements in the identification and validation of such immunological assays and biomarkers, focusing mainly on kidney and liver transplantation. From the published findings so far, it has become clear that indicative biomarkers may vary between different therapeutic approaches applied and organs transplanted. Also, patient numbers studied so far are very small. This is the main reason why nearly all described parameters lack validation and reproducibility testing in large clinical trials, and are therefore not yet suitable for clinical practice.
[Mh] Termos MeSH primário: Sobrevivência de Enxerto
Imunossupressores/uso terapêutico
Transplante de Fígado
Monitorização Imunológica/métodos
Tolerância ao Transplante
[Mh] Termos MeSH secundário: Animais
Biomarcadores
Seres Humanos
Imunossupressores/efeitos adversos
Transplante Homólogo
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Biomarkers); 0 (Immunosuppressive Agents)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170803
[Lr] Data última revisão:
170803
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170519
[St] Status:MEDLINE
[do] DOI:10.1111/cei.12988


  6 / 2188 MEDLINE  
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[PMID]:28422925
[Au] Autor:Gao B; Gu Y; Rong C; Moore C; Porcheray F; Wong W; Preffer F; Saidman SL; Fu Y; Cosimi B; Sachs DH; Kawai T; Sykes M; Zorn E
[Ad] Endereço:1 Transplant Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA. 2 Transplant Center, The First Hospital of Jilin University, Changchun, China. 3 Columbia Center for Translational Immunology, Department of Medicine, Columbia University Medical Center, New York, NY. 4 The Affiliated Hospital to Changchun University of Chinese Medicine, Changchun, China. 5 Department of Pathology, Massachusetts General Hospital, Harvard Medical School, Boston, MA.
[Ti] Título:Dynamics of B Cell Recovery In Kidney/Bone Marrow Transplant Recipients.
[So] Source:Transplantation;101(11):2722-2730, 2017 Nov.
[Is] ISSN:1534-6080
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Previous studies identified B cell gene signatures and predominance of specific B cell subsets as a marker of operational tolerance after kidney transplantation. These findings suggested a role for B cells in the establishment or maintenance of tolerance. Here we analyzed B cell recovery in 4 subjects, 3 of whom achieved tolerance after combined kidney/bone marrow transplantation. METHODS: Peripheral B cell subsets were examined longitudinally by flow cytometry. Immunoglobulin heavy chain repertoire analysis was performed using next-generation sequencing. Lastly, the patients' serum reactivity to HLA was assessed by Luminex. RESULTS: B cell counts recovered approximately 1 year posttransplant except for 1 subject who experienced delayed reconstitution. This subject resumed immunosuppression for acute rejection at 10 months posttransplant and underwent preemptive retransplantation at 3 years for chronic rejection. B cell recovery was accompanied by a high frequency of CD20 + CD24CD38 transitional B cells and a diversified clonal repertoire. However, all 4 subjects showed prevalence of CD20 + CD27+ memory B cells around 6 months posttransplant when B cell counts were still low and the clonal B cell repertoire very limited. The predominance of memory B cells was also associated with high levels of somatically mutated immunoglobulin heavy chain variable sequences and transient serum reactivity to HLA. CONCLUSIONS: Our observations reveal the presence of memory B cells early posttransplant that likely escaped the preparative regimen at a time consistent with the establishment of tolerance. Further studies are warranted to characterize the functional properties of these persisting memory cells and evaluate their potential contribution to tolerance induction.
[Mh] Termos MeSH primário: Linfócitos B/imunologia
Transplante de Medula Óssea
Proliferação Celular
Transplante de Rim
[Mh] Termos MeSH secundário: Linfócitos B/metabolismo
Biomarcadores/sangue
Boston
Feminino
Genes de Cadeia Pesada de Imunoglobulina
Sobrevivência de Enxerto
Antígenos HLA/imunologia
Hospitais Gerais
Seres Humanos
Memória Imunológica
Isoanticorpos/sangue
Contagem de Linfócitos
Masculino
Mutação
Fenótipo
Recuperação de Função Fisiológica
Fatores de Tempo
Tolerância ao Transplante
Resultado do Tratamento
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Biomarkers); 0 (HLA Antigens); 0 (Isoantibodies)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171106
[Lr] Data última revisão:
171106
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170420
[St] Status:MEDLINE
[do] DOI:10.1097/TP.0000000000001789


  7 / 2188 MEDLINE  
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[PMID]:28422316
[Au] Autor:Vaikunthanathan T; Safinia N; Boardman D; Lechler RI; Lombardi G
[Ad] Endereço:MRC Centre for Transplantation, Division of Transplantation Immunology and Mucosal Biology, King's College London, London, UK.
[Ti] Título:Regulatory T cells: tolerance induction in solid organ transplantation.
[So] Source:Clin Exp Immunol;189(2):197-210, 2017 Aug.
[Is] ISSN:1365-2249
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:The concept of regulatory T cell (T ) therapy in transplantation is now a reality. Significant advances in science and technology have enabled us to isolate human T , expand them to clinically relevant numbers and infuse them into human transplant recipients. With several Phase I/II trials under way investigating T safety and efficacy it is now more crucial than ever to understand their complex biology. However, our journey is by no means complete; results from these trials will undoubtedly provoke both further knowledge and enquiry which, alongside evolving science, will continue to drive the optimization of T therapy in the pursuit of transplantation tolerance. In this review we will summarize current knowledge of T biology, explore novel technologies in the setting of T immunotherapy and address key prerequisites surrounding the clinical application of T in transplantation.
[Mh] Termos MeSH primário: Imunidade Adaptativa
Rejeição de Enxerto/tratamento farmacológico
Imunoterapia/métodos
Transplante de Órgãos
Linfócitos T Reguladores/imunologia
Tolerância ao Transplante
[Mh] Termos MeSH secundário: Animais
Ensaios Clínicos como Assunto
Criopreservação
Seres Humanos
Imunossupressores/uso terapêutico
Camundongos
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Immunosuppressive Agents)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170803
[Lr] Data última revisão:
170803
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170420
[St] Status:MEDLINE
[do] DOI:10.1111/cei.12978


  8 / 2188 MEDLINE  
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[PMID]:28395110
[Au] Autor:Mahr B; Wekerle T
[Ad] Endereço:Section of Transplantation Immunology, Department of Surgery, Medical University of Vienna, Vienna, Austria.
[Ti] Título:Murine models of transplantation tolerance through mixed chimerism: advances and roadblocks.
[So] Source:Clin Exp Immunol;189(2):181-189, 2017 Aug.
[Is] ISSN:1365-2249
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Organ transplantation is the treatment of choice for patients with end-stage organ failure, but chronic immunosuppression is taking its toll in terms of morbidity and poor efficacy in preventing late graft loss. Therefore, a drug-free state would be desirable where the recipient permanently accepts a donor organ while remaining otherwise fully immunologically competent. Mouse studies unveiled mixed chimerism as an effective approach to induce such donor-specific tolerance deliberately and laid the foundation for a series of clinical pilot trials. Nevertheless, its widespread clinical implementation is currently prevented by cytotoxic conditioning and limited efficacy. Therefore, the use of mouse studies remains an indispensable tool for the development of novel concepts with potential for translation and for the delineation of underlying tolerance mechanisms. Recent innovations developed in mice include the use of pro-apoptotic drugs or regulatory T cell (T ) transfer for promoting bone marrow engraftment in the absence of myelosuppression and new insight gained in the role of innate immunity and the interplay between deletion and regulation in maintaining tolerance in chimeras. Here, we review these and other recent advances in murine studies inducing transplantation tolerance through mixed chimerism and discuss both the advances and roadblocks of this approach.
[Mh] Termos MeSH primário: Transplante de Medula Óssea
Linfócitos T Reguladores/imunologia
Quimeras de Transplante/imunologia
Condicionamento Pré-Transplante/métodos
Tolerância ao Transplante
[Mh] Termos MeSH secundário: Animais
Modelos Animais de Doenças
Seres Humanos
Camundongos
Transplante Homólogo
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170803
[Lr] Data última revisão:
170803
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170411
[St] Status:MEDLINE
[do] DOI:10.1111/cei.12976


  9 / 2188 MEDLINE  
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[PMID]:28376037
[Au] Autor:Lam AJ; Hoeppli RE; Levings MK
[Ad] Endereço:1 Department of Surgery, University of British Columbia and British Columbia Children's Hospital Research Institute, Vancouver, BC, Canada.
[Ti] Título:Harnessing Advances in T Regulatory Cell Biology for Cellular Therapy in Transplantation.
[So] Source:Transplantation;101(10):2277-2287, 2017 Oct.
[Is] ISSN:1534-6080
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Cellular therapy with CD4FOXP3 T regulatory (Treg) cells is a promising strategy to induce tolerance after solid-organ transplantation or prevent graft-versus-host disease after transfer of hematopoietic stem cells. Treg cells currently used in clinical trials are either polyclonal, donor- or antigen-specific. Aside from variations in isolation and expansion protocols, however, most therapeutic Treg cell-based products are much alike. Ongoing basic science work has provided considerable new insight into multiple facets of Treg cell biology, including their stability, homing, and functional specialization; integrating these basic science discoveries with clinical efforts will support the development of next-generation therapeutic Treg cells with enhanced efficacy. In this review, we summarize recent advances in knowledge of how Treg cells home to lymphoid and peripheral tissues, and control antibody production and tissue repair. We also discuss newly appreciated pathways that modulate context-specific Treg cell function and stability. Strategies to improve and tailor Treg cells for cell therapy to induce transplantation tolerance are highlighted.
[Mh] Termos MeSH primário: Transferência Adotiva/tendências
Alergia e Imunologia/tendências
Rejeição de Enxerto/prevenção & controle
Transplante de Órgãos/tendências
Linfócitos T Reguladores/transplante
[Mh] Termos MeSH secundário: Animais
Linfócitos B/imunologia
Quimiotaxia de Leucócito
Difusão de Inovações
Previsões
Terapia Genética/métodos
Rejeição de Enxerto/imunologia
Sobrevivência de Enxerto
Seres Humanos
Transplante de Órgãos/efeitos adversos
Fenótipo
Receptores de Antígenos de Linfócitos T/genética
Receptores de Antígenos de Linfócitos T/imunologia
Receptores de Antígenos de Linfócitos T/metabolismo
Linfócitos T Auxiliares-Indutores/imunologia
Linfócitos T Reguladores/imunologia
Linfócitos T Reguladores/metabolismo
Tolerância ao Transplante
Resultado do Tratamento
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Receptors, Antigen, T-Cell)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171016
[Lr] Data última revisão:
171016
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170405
[St] Status:MEDLINE
[do] DOI:10.1097/TP.0000000000001757


  10 / 2188 MEDLINE  
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[PMID]:28369830
[Au] Autor:Oura T; Cosimi AB; Kawai T
[Ad] Endereço:Department of Surgery, Center for Transplantation Sciences, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
[Ti] Título:Chimerism-based tolerance in organ transplantation: preclinical and clinical studies.
[So] Source:Clin Exp Immunol;189(2):190-196, 2017 Aug.
[Is] ISSN:1365-2249
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Induction of allograft tolerance has been considered the ultimate goal in organ transplantation. Although numerous protocols to induce allograft tolerance have been reported in mice, a chimerism-based approach through donor haematopoietic stem cell transplantation has been the only approach to date that induced allograft tolerance reproducibly following kidney transplantation in man. Renal allograft tolerance has been achieved by induction of either transient mixed chimerism or persistent full donor chimerism. Although the risk of rejection may be low in tolerance achieved via durable full donor chimerism, the development of graft-versus-host disease (GVHD) has limited the wider clinical application of this approach. In contrast, tolerance induced by transient mixed chimerism has not been associated with GVHD, but the risk of allograft rejection is more difficult to predict after the disappearance of haematopoietic chimerism. Current efforts are directed towards the development of more clinically feasible and reliable approaches to induce more durable mixed chimerism in order to widen the clinical applicability of these treatment regimens.
[Mh] Termos MeSH primário: Doença Enxerto-Hospedeiro/imunologia
Transplante de Células-Tronco Hematopoéticas
Quimeras de Transplante/imunologia
Condicionamento Pré-Transplante/métodos
Tolerância ao Transplante
[Mh] Termos MeSH secundário: Animais
Ensaios Clínicos como Assunto
Modelos Animais de Doenças
Sobrevivência de Enxerto
Seres Humanos
Transplante de Rim
Camundongos
Transplante Homólogo
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170803
[Lr] Data última revisão:
170803
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170404
[St] Status:MEDLINE
[do] DOI:10.1111/cei.12969



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