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[PMID]:29443669
[Au] Autor:El-Jawahri AR; Schaefer PW; El Khoury JB; Martinez-Lage M
[Ad] Endereço:From the Departments of Medicine (A.R.E.-J., J.B.E.K.), Radiology (P.W.S.), and Pathology (M.M.-L.), Massachusetts General Hospital, and the Departments of Medicine (A.R.E.-J., J.B.E.K.), Radiology (P.W.S.), and Pathology (M.M.-L.), Harvard Medical School - both in Boston.
[Ti] Título:Case 5-2018: A 63-Year-Old Man with Confusion after Stem-Cell Transplantation.
[So] Source:N Engl J Med;378(7):659-669, 2018 Feb 15.
[Is] ISSN:1533-4406
[Cp] País de publicação:United States
[La] Idioma:eng
[Mh] Termos MeSH primário: Confusão/etiologia
Transplante de Células-Tronco Hematopoéticas/efeitos adversos
Herpesvirus Humano 6/isolamento & purificação
Hospedeiro Imunocomprometido
Meningoencefalite/diagnóstico
Infecções por Roseolovirus/diagnóstico
[Mh] Termos MeSH secundário: Antivirais/uso terapêutico
Autopsia
Diagnóstico Diferencial
Evolução Fatal
Foscarnet/uso terapêutico
Reação Enxerto-Hospedeiro
Seres Humanos
Leucemia Linfocítica Crônica de Células B/terapia
Masculino
Meningoencefalite/complicações
Meningoencefalite/virologia
Meia-Idade
Infecções por Roseolovirus/complicações
Infecções por Roseolovirus/tratamento farmacológico
Transplante Homólogo
[Pt] Tipo de publicação:CASE REPORTS; CLINICAL CONFERENCE; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antiviral Agents); 364P9RVW4X (Foscarnet)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180220
[Lr] Data última revisão:
180220
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:180215
[St] Status:MEDLINE
[do] DOI:10.1056/NEJMcpc1707556


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[PMID]:28067900
[Au] Autor:Ghosh A; Smith M; James SE; Davila ML; Velardi E; Argyropoulos KV; Gunset G; Perna F; Kreines FM; Levy ER; Lieberman S; Jay HV; Tuckett AZ; Zakrzewski JL; Tan L; Young LF; Takvorian K; Dudakov JA; Jenq RR; Hanash AM; Motta AC; Murphy GF; Liu C; Schietinger A; Sadelain M; van den Brink MR
[Ad] Endereço:Department of Medicine and Immunology Program, Memorial Sloan Kettering Cancer Center, New York, New York, USA.
[Ti] Título:Donor CD19 CAR T cells exert potent graft-versus-lymphoma activity with diminished graft-versus-host activity.
[So] Source:Nat Med;23(2):242-249, 2017 Feb.
[Is] ISSN:1546-170X
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a potentially curative therapy for hematological malignancies. However, graft-versus-host disease (GVHD) and relapse after allo-HSCT remain major impediments to the success of allo-HSCT. Chimeric antigen receptors (CARs) direct tumor cell recognition of adoptively transferred T cells. CD19 is an attractive CAR target, which is expressed in most B cell malignancies, as well as in healthy B cells. Clinical trials using autologous CD19-targeted T cells have shown remarkable promise in various B cell malignancies. However, the use of allogeneic CAR T cells poses a concern in that it may increase risk of the occurrence of GVHD, although this has not been reported in selected patients infused with donor-derived CD19 CAR T cells after allo-HSCT. To understand the mechanism whereby allogeneic CD19 CAR T cells may mediate anti-lymphoma activity without causing a significant increase in the incidence of GVHD, we studied donor-derived CD19 CAR T cells in allo-HSCT and lymphoma models in mice. We demonstrate that alloreactive T cells expressing CD28-costimulated CD19 CARs experience enhanced stimulation, resulting in the progressive loss of both their effector function and proliferative potential, clonal deletion, and significantly decreased occurrence of GVHD. Concurrently, the other CAR T cells that were present in bulk donor T cell populations retained their anti-lymphoma activity in accordance with the requirement that both the T cell receptor (TCR) and CAR be engaged to accelerate T cell exhaustion. In contrast, first-generation and 4-1BB-costimulated CAR T cells increased the occurrence of GVHD. These findings could explain the reduced risk of GVHD occurring with cumulative TCR and CAR signaling.
[Mh] Termos MeSH primário: Reação Enxerto-Hospedeiro/imunologia
Efeito Enxerto vs Tumor/imunologia
Transplante de Células-Tronco Hematopoéticas
Linfoma/imunologia
Receptores de Antígenos de Linfócitos T/imunologia
Linfócitos T/imunologia
[Mh] Termos MeSH secundário: Ligante 4-1BB/imunologia
Transferência Adotiva
Animais
Antígenos CD19/metabolismo
Linfócitos B/imunologia
Antígenos CD28
Quimera
Citocinas/imunologia
Modelos Animais de Doenças
Citometria de Fluxo
Doença Enxerto-Hospedeiro/imunologia
Camundongos
Linfócitos T/metabolismo
Transplante Homólogo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (4-1BB Ligand); 0 (Antigens, CD19); 0 (CD28 Antigens); 0 (Cytokines); 0 (Receptors, Antigen, T-Cell)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170110
[St] Status:MEDLINE
[do] DOI:10.1038/nm.4258


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[PMID]:28057181
[Au] Autor:de Fontbrune FS; Cavalieri D; Leclerc M; Beckerich F; Maury S; de Latour RP; N-Guyen S; Bay JO
[Ad] Endereço:Hématologie clinique et transplantation, GH Henri-Mondor, Créteil, France.
[Ti] Título:Immunothérapie et greffe de cellules souches hématopoïétiques allogéniques..
[So] Source:Bull Cancer;103 Suppl 1:S164-S174, 2016 Nov.
[Is] ISSN:1769-6917
[Cp] País de publicação:France
[La] Idioma:fre
[Ab] Resumo:IMMUNOTHERAPY AND ALLOGENEIC STEM CELLS TRANSPLANTATION: Allogeneic stem cell transplantations represent perfect example of immunotherapy. Its positive aspects are due to the graft versus tumor effect. Unfortunately, this therapeutic advantage is usually associated with graft versus host effects. While the mechanism of these two graft reactions remain unclear, this is possible to modulate these immunologic effects. The type of conditioning regimen, the source of donor and the use of donor cells after the transplantation may influence the toxicity and the tumor response, leading to a better optimization of the procedure. This paper is presenting all the parameters which may contribute to improve allogeneic stem cell transplantations.
[Mh] Termos MeSH primário: Efeito Enxerto vs Tumor/imunologia
Antígenos HLA/imunologia
Transplante de Células-Tronco Hematopoéticas
Imunoterapia/métodos
Condicionamento Pré-Transplante
[Mh] Termos MeSH secundário: Reação Enxerto-Hospedeiro/imunologia
Transplante de Células-Tronco Hematopoéticas/efeitos adversos
Histocompatibilidade/genética
Histocompatibilidade/imunologia
Seres Humanos
Imunomodulação
Imunoterapia/efeitos adversos
Células Matadoras Naturais/imunologia
Linfócitos T/imunologia
Linfócitos T Reguladores/imunologia
Transplante Homólogo/efeitos adversos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (HLA Antigens)
[Em] Mês de entrada:1701
[Cu] Atualização por classe:170624
[Lr] Data última revisão:
170624
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170107
[St] Status:MEDLINE


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[PMID]:27447289
[Au] Autor:Alhuraiji A; Alzahrani H; Al Mohareb F; Chaudhri N; Alsharif F; Mohamed S; Rasheed W; Aldawsari G; Ahmed SO; Aljurf M
[Ti] Título:Hematopoietic Stem Cell Transplant in Adolescent and Young Adults With Fanconi Anemia Is Feasible With Acceptable Toxicity, With Those Surviving 100 Days Posttransplant Having Excellent Outcomes.
[So] Source:Exp Clin Transplant;14(6):660-664, 2016 12.
[Is] ISSN:2146-8427
[Cp] País de publicação:Turkey
[La] Idioma:eng
[Ab] Resumo:OBJECTIVES: Fanconi anemia is a congenital bone marrow failure syndrome that is associated with congenital anomalies and increased risk of cancer. Hematopoietic stem cell transplant is a potentially curative modality for bone marrow failure in Fanconi anemia patients. Here, we report our center's experience regarding adolescent and young adult patients with Fanconi anemia and hematopoietic stem cell transplant. MATERIALS AND METHODS: We conducted a retrospective patient record analyses of patients who presented at our center from 1988 to 2014. We included patients greater than 14 years old with confirmed Fanconi anemia based on positive chromosome breakage study and who underwent hematopoietic stem cell transplant at our institution. RESULTS: Our study group comprised 12 patients with Fanconi anemia who underwent hematopoietic stem cell transplant at our institution. The median age was 20 years (range, 14-31 y) with a female predominance of 83%. Low-dose cyclophosphamide (20-80 mg/kg)-based conditioning regimens were used with different combinations that included fludarabine, antithymocyte globulin, or total body irradiation. All patients had HLA-matched sibling grafts. In all patients, stem cell source was the bone marrow. All patients showed engraftment. Four patients (33%) developed acute graft-versus-host disease. Three patients (25%) died early before day 100 after hematopoietic stem cell transplant due to infectious complications, with 1 patient having steroid refractory acute graft-versus-host disease. Overall survival was 75% at a median follow-up of 43 months. All patients who survived are well and remained transfusion independent without evidence of secondary malignancy. CONCLUSIONS: Our findings support the feasibility of reduced intensity conditioning allogeneic hematopoietic stem cell transplant in older and more heavily pretreated patients with Fanconi anemia, especially for those who are engrafted.
[Mh] Termos MeSH primário: Anemia de Fanconi/terapia
Transplante de Células-Tronco Hematopoéticas
Complicações Pós-Operatórias/tratamento farmacológico
Complicações Pós-Operatórias/mortalidade
Condicionamento Pré-Transplante
[Mh] Termos MeSH secundário: Adolescente
Adulto
Transplante de Medula Óssea
Anemia de Fanconi/mortalidade
Feminino
Reação Enxerto-Hospedeiro
Seres Humanos
Masculino
Complicações Pós-Operatórias/imunologia
Estudos Retrospectivos
Análise de Sobrevida
Taxa de Sobrevida
Fatores de Tempo
Adulto Jovem
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170817
[Lr] Data última revisão:
170817
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160723
[St] Status:MEDLINE
[do] DOI:10.6002/ect.2015.0364


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[PMID]:27152919
[Au] Autor:Qesari M; Richter A; Ogonek J; Mischak-Weissinger E; Wang XN; Dickinson AM
[Ad] Endereço:1 Alcyomics Ltd, Newcastle upon Tyne, United Kingdom. Haematological Sciences, Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, United Kingdom. 2 Miltenyi Biotec GmbH, Bergisch Gladbach, Germany. 3 Department of Hematology, Hemostasis, Oncology and Stem Cell Transplantation, Hannover Medical School (MHH), Hannover, Germany. 4 Haematological Sciences, Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, United Kingdom.
[Ti] Título:Cytomegalovirus-Specific T Cells Isolated by IFN-γ Secretion Assay Do Not Induce Significant Graft-Versus-Host Reactions In Vitro.
[So] Source:Transplantation;100(11):2352-2361, 2016 Nov.
[Is] ISSN:1534-6080
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Graft-versus-host (GvH) disease (GvHD) remains a serious concern for patients undergoing antiviral cellular therapy. Despite the major improvements in cellular immunotherapy, the immunogenicity of virus-specific T cells has not yet been fully defined. This present study aims to examine how cytomegalovirus (CMV)-specific cytotoxic T lymphocytes (CTLs) respond to allogeneic antigen stimulation and whether they give rise to GvHD target tissue damage. METHODS: Cytomegalovirus-specific CTLs were isolated by the IFN-γ secretion assay (gamma-catch) from healthy seropositive volunteers and expanded in vitro. The levels of intracellular IFN-γ, cytotoxic activity, IFN-γ and granzyme B secretion, and CD25 expression were measured using flow cytometry (fluorescence-activated cell sorting). The ability of CMV-CTLs to induce GvHD target tissue damage was evaluated using the human in vitro skin explant assay (skin explant assay). RESULTS: Cytomegalovirus-specific CTLs responded specifically to CMV-phosphoprotein 65 stimulation by secreting IFN-γ and killing virus peptide loaded autologous phytohemagglutinin (PHA) blasts. Compared with unselected peripheral blood mononuclear cells, CMV-CTLs induced significantly less severe cutaneous GvH tissue damage. This observation coincided with low levels of CD25 expression, as well as IFN-γ and granzyme B secretion after allogeneic antigen stimulation in both the mixed lymphocyte reaction and in the skin explant assay. CONCLUSIONS: Cytomegalovirus-specific CTLs isolated by the IFN-γ secretion assay from HLA-unmatched healthy donors exhibited a high level of anti-CMV potency without inducing significant cutaneous GvH tissue damage in vitro. This finding provides novel evidence supporting the safe use of in vitro expanded CMV-CTLs as an antiviral therapy in transplant patients with refractory CMV infections.
[Mh] Termos MeSH primário: Citomegalovirus/imunologia
Reação Enxerto-Hospedeiro
Interferon gama/secreção
Linfócitos T Citotóxicos/imunologia
[Mh] Termos MeSH secundário: Linfócitos T CD4-Positivos/imunologia
Granzimas/secreção
Seres Humanos
Técnicas In Vitro
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
82115-62-6 (Interferon-gamma); EC 3.4.21.- (Granzymes)
[Em] Mês de entrada:1705
[Cu] Atualização por classe:170517
[Lr] Data última revisão:
170517
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160507
[St] Status:MEDLINE


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[PMID]:26522814
[Au] Autor:Sahoo S; Sengupta D
[Ad] Endereço:Department of Statistics, Haldia Government College, Haldia, 721657, India.
[Ti] Título:On graphical tests for proportionality of hazards in two samples.
[So] Source:Stat Med;35(6):942-56, 2016 Mar 15.
[Is] ISSN:1097-0258
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:In this paper, we present a class of graphical tests of the proportional hazards hypothesis for two-sample censored survival data. The proposed tests are improvements over some existing tests based on asymptotic confidence bands of certain functions of the estimated cumulative hazard functions. The new methods are based on the comparison of unrestricted estimates of the said functions and their restricted versions under the hypothesis. They combine the rigour of analytical tests with the descriptive value of plots. Monte Carlo simulations suggest that the proposed asymptotic procedures have reasonable small sample properties. The power is much higher than existing graphical tests and comparable with existing analytical tests. The method is then illustrated through the analysis of a data set on bone marrow transplantation for Leukemia patients.
[Mh] Termos MeSH primário: Transplante de Medula Óssea/estatística & dados numéricos
Reação Enxerto-Hospedeiro/efeitos dos fármacos
Leucemia/terapia
Modelos de Riscos Proporcionais
Análise de Sobrevida
[Mh] Termos MeSH secundário: Transplante de Medula Óssea/efeitos adversos
Transplante de Medula Óssea/métodos
Simulação por Computador
Seres Humanos
Imunossupressores/administração & dosagem
Leucemia/mortalidade
Metotrexato/administração & dosagem
Estudos Multicêntricos como Assunto
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Immunosuppressive Agents); YL5FZ2Y5U1 (Methotrexate)
[Em] Mês de entrada:1610
[Cu] Atualização por classe:161230
[Lr] Data última revisão:
161230
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:151103
[St] Status:MEDLINE
[do] DOI:10.1002/sim.6781


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[PMID]:26742237
[Au] Autor:Lücker LM; Rochat T; Masouridi-Levrat S; Adler D
[Ti] Título:[Non-infectious lung diseases after hematopoietic stem cell transplantation].
[Ti] Título:Pathologies pulmonaires non infectieuses après transplantation de cellules-souches hématopoïétiques..
[So] Source:Rev Med Suisse;11(495):2163-6, 2168-9, 2015 Nov 18.
[Is] ISSN:1660-9379
[Cp] País de publicação:Switzerland
[La] Idioma:fre
[Ab] Resumo:Non-infectious pulmonary complications following hematopoietic stem cell transplantation are entities occuring early or late, depending on whether they occur before or after 100 days post-transplantation. They have firstly to be differentiated from infectious complications, which is not always easy, as their clinical and radiological aspects can mimic a viral or bacterial pneumonia. Corticosteroids are the most given treatment but a significant subset of patients have a fatal outcome. This article will review the clinical, radiological, functionnal features and the therapeutic options of six entities (engraftment syndrome, diffuse alveolar hemorrage, idiopathic pneumonia syndrome, organizing pneumonia, bronchiolitis obliterans, post-transplantation lympho-proliferative disease).
[Mh] Termos MeSH primário: Transplante de Células-Tronco Hematopoéticas/efeitos adversos
Pneumopatias/etiologia
[Mh] Termos MeSH secundário: Reação Enxerto-Hospedeiro
Seres Humanos
[Pt] Tipo de publicação:ENGLISH ABSTRACT; JOURNAL ARTICLE
[Em] Mês de entrada:1602
[Cu] Atualização por classe:160108
[Lr] Data última revisão:
160108
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160109
[St] Status:MEDLINE


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[PMID]:26544708
[Au] Autor:Shearer GM; Clerici M; Graham DR; Boasso A
[Ad] Endereço:aExperimental Immunology Branch, Center for Cancer Research, National Institutes of Health, Bethesda, Maryland, USA bDepartment of Physiopathology and Transplants, University of Milano cDon C. Gnocchi Foundation ONLUS, IRCCS, Milano, Italy dDepartment of Molecular and Comparative Pathobiology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA eCentre for Immunology and Vaccinology, Chelsea and Westminster Hospital, Imperial College London, London, UK.
[Ti] Título:Curing HIV/AIDS beyond hematopoietic stem cell transplant.
[So] Source:AIDS;29(17):2364-6, 2015 Nov.
[Is] ISSN:1473-5571
[Cp] País de publicação:England
[La] Idioma:eng
[Mh] Termos MeSH primário: Infecções por HIV/terapia
Transplante de Células-Tronco Hematopoéticas/métodos
Transplante Homólogo/métodos
[Mh] Termos MeSH secundário: Reação Enxerto-Hospedeiro
Seres Humanos
Resultado do Tratamento
[Pt] Tipo de publicação:LETTER
[Em] Mês de entrada:1608
[Cu] Atualização por classe:151107
[Lr] Data última revisão:
151107
[Sb] Subgrupo de revista:IM; X
[Da] Data de entrada para processamento:151107
[St] Status:MEDLINE
[do] DOI:10.1097/QAD.0000000000000861


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[PMID]:26085679
[Au] Autor:Li HW; Andreola G; Carlson AL; Shao S; Lin CP; Zhao G; Sykes M
[Ad] Endereço:Columbia Center for Translational Immunology, Columbia University Medical Center, New York, NY 10032; Transplantation Biology Research Center, Massachusetts General Hospital/Harvard Medical School, Boston, MA 02129;
[Ti] Título:Rapid Functional Decline of Activated and Memory Graft-versus-Host-Reactive T Cells Encountering Host Antigens in the Absence of Inflammation.
[So] Source:J Immunol;195(3):1282-92, 2015 Aug 01.
[Is] ISSN:1550-6606
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Inflammation in the priming host environment has critical effects on the graft-versus-host (GVH) responses mediated by naive donor T cells. However, it is unclear how a quiescent or inflammatory environment impacts the activity of GVH-reactive primed T and memory cells. We show in this article that GVH-reactive primed donor T cells generated in irradiated recipients had diminished ability compared with naive T cells to increase donor chimerism when transferred to quiescent mixed allogeneic chimeras. GVH-reactive primed T cells showed marked loss of cytotoxic function and activation, and delayed but not decreased proliferation or accumulation in lymphoid tissues when transferred to quiescent mixed chimeras compared with freshly irradiated secondary recipients. Primed CD4 and CD8 T cells provided mutual help to sustain these functions in both subsets. CD8 help for CD4 cells was largely IFN-γ dependent. TLR stimulation after transfer of GVH-reactive primed T cells to mixed chimeras restored their cytotoxic effector function and permitted the generation of more effective T cell memory in association with reduced PD-1 expression on CD4 memory cells. Our data indicate that an inflammatory host environment is required for the maintenance of GVH-reactive primed T cell functions and the generation of memory T cells that can rapidly acquire effector functions. These findings have important implications for graft-versus-host disease and T cell-mediated immunotherapies.
[Mh] Termos MeSH primário: Linfócitos T CD4-Positivos/imunologia
Linfócitos T CD8-Positivos/imunologia
Reação Enxerto-Hospedeiro/imunologia
Inflamação/imunologia
Ativação Linfocitária/imunologia
[Mh] Termos MeSH secundário: Animais
Apoptose/imunologia
Linfócitos T CD4-Positivos/transplante
Linfócitos T CD8-Positivos/transplante
Proliferação Celular
Feminino
Memória Imunológica/imunologia
Interferon gama/imunologia
Camundongos
Camundongos Endogâmicos C57BL
Camundongos Knockout
Receptor de Morte Celular Programada 1/biossíntese
Quimera por Radiação/imunologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Pdcd1 protein, mouse); 0 (Programmed Cell Death 1 Receptor); 82115-62-6 (Interferon-gamma)
[Em] Mês de entrada:1510
[Cu] Atualização por classe:161019
[Lr] Data última revisão:
161019
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:150619
[St] Status:MEDLINE
[do] DOI:10.4049/jimmunol.1401511


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[PMID]:26034207
[Au] Autor:Sido JM; Nagarkatti PS; Nagarkatti M
[Ad] Endereço:*Department of Pathology, Microbiology, and Immunology, University of South Carolina School of Medicine, Columbia, South Carolina, USA; and William Jennings Bryan Dorn Veterans Affairs Medical Center, Columbia, South Carolina, USA.
[Ti] Título:Δ9-Tetrahydrocannabinol attenuates allogeneic host-versus-graft response and delays skin graft rejection through activation of cannabinoid receptor 1 and induction of myeloid-derived suppressor cells.
[So] Source:J Leukoc Biol;98(3):435-47, 2015 Sep.
[Is] ISSN:1938-3673
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Immune cells have been shown to express cannabinoid receptors and to produce endogenous ligands. Moreover, activation of cannabinoid receptors on immune cells has been shown to trigger potent immunosuppression. Despite such studies, the role of cannabinoids in transplantation, specifically to prevent allograft rejection, has not, to our knowledge, been investigated previously. In the current study, we tested the effect of THC on the suppression of HvGD as well as rejection of skin allografts. To this end, we studied HvGD by injecting H-2(k) splenocytes into H-2(b) mice and analyzing the immune response in the draining ingLNs. THC treatment significantly reduced T cell proliferation and activation in draining LNs of the recipient mice and decreased early stage rejection-indicator cytokines, including IL-2 and IFN-γ. THC treatment also increased the allogeneic skin graft survival. THC treatment in HvGD mice led to induction of MDSCs. Using MDSC depletion studies as well as adoptive transfer experiments, we found that THC-induced MDSCs were necessary for attenuation of HvGD. Additionally, using pharmacological inhibitors of CB1 and CB2 receptors and CB1 and CB2 knockout mice, we found that THC was working preferentially through CB1. Together, our research shows, for the first time to our knowledge, that targeting cannabinoid receptors may provide a novel treatment modality to attenuate HvGD and prevent allograft rejection.
[Mh] Termos MeSH primário: Dronabinol/farmacologia
Rejeição de Enxerto/imunologia
Rejeição de Enxerto/prevenção & controle
Reação Enxerto-Hospedeiro/imunologia
Células Mieloides/patologia
Receptor CB1 de Canabinoide/metabolismo
Transplante de Pele
[Mh] Termos MeSH secundário: Transferência Adotiva
Animais
Proliferação Celular/efeitos dos fármacos
Citocinas/metabolismo
Dronabinol/administração & dosagem
Feminino
Sobrevivência de Enxerto/efeitos dos fármacos
Sobrevivência de Enxerto/imunologia
Reação Enxerto-Hospedeiro/efeitos dos fármacos
Tolerância Imunológica/efeitos dos fármacos
Inflamação/patologia
Mediadores da Inflamação/metabolismo
Linfonodos/efeitos dos fármacos
Linfonodos/patologia
Ativação Linfocitária/efeitos dos fármacos
Camundongos Endogâmicos C57BL
Células Mieloides/efeitos dos fármacos
Células Mieloides/metabolismo
Transplante Homólogo
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL; RESEARCH SUPPORT, U.S. GOV'T, NON-P.H.S.
[Nm] Nome de substância:
0 (Cytokines); 0 (Inflammation Mediators); 0 (Receptor, Cannabinoid, CB1); 7J8897W37S (Dronabinol)
[Em] Mês de entrada:1511
[Cu] Atualização por classe:170220
[Lr] Data última revisão:
170220
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:150603
[St] Status:MEDLINE
[do] DOI:10.1189/jlb.3A0115-030RR



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