Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 53
Filtrar
Mais filtros

Base de dados
País/Região como assunto
Tipo de documento
País de afiliação
Intervalo de ano de publicação
1.
Clin Exp Immunol ; 188(2): 275-282, 2017 05.
Artigo em Inglês | MEDLINE | ID: mdl-28142207

RESUMO

Splenic macrophages play a key role in immune thrombocytopenia (ITP) pathogenesis by clearing opsonized platelets. Fcγ receptors (FcγR) participate in this phenomenon, but their expression on splenic macrophages and their modulation by treatment have scarcely been studied in human ITP. We aimed to compare the phenotype and function of splenic macrophages between six controls and 24 ITP patients and between ITP patients according to the treatments they received prior to splenectomy. CD86, human leucocyte antigen D-related (HLA-DR) and FcγR expression were measured by flow cytometry on splenic macrophages. The major FcγR polymorphisms were determined and splenic macrophage function was assessed by a phagocytosis assay. The expression of the activation markers CD86 and HLA-DR was higher on splenic macrophages during ITP compared to controls. While the expression of FcγR was not different between ITP and controls, the phagocytic function of splenic macrophages was reduced in ITP patients treated with intravenous immunoglobulin (IVIg) within the 2 weeks prior to splenectomy. The FCGR3A (158V/F) polymorphism, known to increase the affinity of FcγRIII to IgG, was over-represented in ITP patients. Thus, these are the first results arguing for the fact that the therapeutic use of IVIg during human chronic ITP does not modulate FcγR expression on splenic macrophages but decreases their phagocytic capabilities.


Assuntos
Doenças Autoimunes/imunologia , Macrófagos/imunologia , Receptores de IgG/análise , Receptores de IgG/genética , Baço/imunologia , Trombocitopenia/imunologia , Adulto , Idoso , Doenças Autoimunes/cirurgia , Doenças Autoimunes/terapia , Antígeno B7-2/análise , Feminino , Citometria de Fluxo , Humanos , Imunoglobulina G/sangue , Imunoglobulinas Intravenosas/uso terapêutico , Macrófagos/fisiologia , Masculino , Pessoa de Meia-Idade , Fagocitose , Fenótipo , Polimorfismo Genético , Receptores de IgG/imunologia , Baço/citologia , Esplenectomia , Trombocitopenia/cirurgia , Trombocitopenia/terapia
2.
Transpl Infect Dis ; 18(3): 415-22, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-27027787

RESUMO

BACKGROUND: End-stage renal disease (ESRD) is associated with premature aging of the T-cell system. Nevertheless, the clinical significance of pre-transplant ESRD-related immune senescence is unknown. METHODS: We studied whether immune risk phenotype (IRP), a typical feature of immune senescence, may affect post-transplant infectious complications. A total of 486 patients were prospectively studied during the first year post transplant. IRP was defined as positive cytomegalovirus serology with at least 1 of the following criteria: CD4/CD8 ratio <1 and/or CD8 T-cell count >90th percentile. RESULTS: We found that 47 patients (9.7%) had pre-transplant IRP. IRP+ patients did not differ from IRP- patients for any clinical characteristics, but exhibited more pronounced immune senescence. Both opportunistic infections (43% vs. 6%, P < 0.001) and severe bacterial infection (SBI) (40% vs. 25%, P = 0.028) were more frequent in IRP(+) patients. In multivariate analysis, IRP was predictive of both opportunistic infection (hazard ratio [HR] 2.97 [95% confidence interval {CI} 1.53-5.76], P = 0.001), and SBI (HR 2.33 [95% CI 1.34-3.92], P = 0.008). Acute rejection rates were numerically much lower in IRP+ patients. A total of 418 patients (86%) had biological evaluation 1 year post transplant. Among 41 IRP+ patients, 35 (85%) remained IRP+ 1 year post transplant. CONCLUSION: Pre-transplant IRP is associated with an increased risk of post-transplant infection.


Assuntos
Infecções por Citomegalovirus/tratamento farmacológico , Citomegalovirus/imunologia , Falência Renal Crônica/imunologia , Transplante de Rim/efeitos adversos , Complicações Pós-Operatórias/imunologia , Adulto , Idoso , Infecções por Citomegalovirus/prevenção & controle , Infecções por Citomegalovirus/virologia , Feminino , Rejeição de Enxerto/imunologia , Humanos , Rim/cirurgia , Rim/virologia , Falência Renal Crônica/virologia , Masculino , Pessoa de Meia-Idade , Infecções Oportunistas , Fatores de Risco , Linfócitos T/imunologia , Transplantados
3.
Am J Transplant ; 15(4): 1028-38, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25758660

RESUMO

Persistent ATG-induced CD4(+) T cell lymphopenia is associated with serious clinical complications. We tested the hypothesis that ATG induces accelerated immune senescence in renal transplant recipients (RTR). Immune senescence biomarkers were analyzed at transplant and one-year later in 97 incident RTR -62 patients receiving ATG and 35 receiving anti-CD25 mAb (α-CD25). This consisted in: (i) thymic output; (ii) bone marrow renewal of CD34(+) hematopoietic progenitor cells (CD34(+) HPC) and lymphoid (l-HPC) and myeloid (m-HPC) progenitor ratio; (iii) T cell phenotype; and (iv) measurement of T cell relative telomere length (RTL) and telomerase activity (RTA). Clinical correlates were analyzed with a 3 year follow-up. Thymic output significantly decreased one-year posttransplant in ATG-treated patients. ATG was associated with a significant decrease in l-HPC/m-HPC ratio. Late stage differentiated CD57(+) /CD28(-) T cells increased in ATG-treated patients. One-year posttransplant T cell RTL and RTA were consequently lower in ATG-treated patients. ATG is associated with accelerated immune senescence. Increased frequency of late differentiated CD4(+) T cell frequency at transplantation tended to be predictive of a higher risk of subsequent opportunistic infections and of acute rejection only in ATG-treated patients but this needs confirmation. Considering pretransplant immune profile may help to select those patients who may benefit from ATG to prevent severe infections and acute rejection.


Assuntos
Soro Antilinfocitário/imunologia , Transplante de Rim , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Linfócitos T/imunologia
4.
Pathol Biol (Paris) ; 62(3): 156-61, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24875455

RESUMO

Hematopoietic cell transplantation (HCT) is a curative treatment for hematological malignancies. This therapeutic approach is associated with a profound immune deficiency and an increased rate of opportunistic infections. Nocardiosis is a rare bacterial infection occurring mainly in patients with deficient cell-mediated immunity, such as AIDS patients or transplant recipients. Diagnosis of nocardiosis can be challenging, as signs and symptoms are non-specific. Routine prophylaxis with trimethoprin/sulfamethoxazole (TMP/SMZ) does not prevent the risk of infection. Between May 2001 and December 2009, five cases of nocardiosis were diagnosed from the 366 allogeneic HCT recipients in our centre. Four patients developed a disseminated nocardiosis within the first year after HCT. The fifth patient presented a localized cutaneous nocardiosis. In disseminated cases, median total CD4+ T-cells were below 100 cells/µL. Naive CD4+ CD45RA+/RO- T-cells were almost undetectable. CD8(+) T-cells and NK cells were below the normal range and CD19+ B-cell reconstitution was completely deficient. In a localized case, we observed a lack of naive thymic emigrants CD4+ CD45RA+/RO- T-cells.


Assuntos
Transplante de Medula Óssea , Linfopenia/complicações , Nocardiose/tratamento farmacológico , Adulto , Aloenxertos/imunologia , Anemia Refratária com Excesso de Blastos/terapia , Antibioticoprofilaxia , Contagem de Linfócito CD4 , Linfócitos T CD8-Positivos/imunologia , Função Retardada do Enxerto , Feminino , Sobrevivência de Enxerto , Neoplasias Hematológicas/terapia , Hematopoese , Humanos , Células Matadoras Naturais/imunologia , Contagem de Linfócitos , Subpopulações de Linfócitos/imunologia , Masculino , Pessoa de Meia-Idade , Nocardiose/etiologia , Nocardiose/imunologia
5.
Cell Tissue Bank ; 15(2): 251-5, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24515295

RESUMO

Prevalence of leg ulcer in general population is important and new efficient treatments are now needed, especially for chronic leg ulcers. Human amniotic membrane (HAM) can be used as an alternative treatment for recalcitrant leg ulcers. The aim of this study is to investigate the effects of a HAM extract on normal fibroblasts (NF) and ulcer fibroblasts (UF). NF and UF were obtained from biopsies by explants technique. HAM extract was used at 10 µg of total proteins per ml. Single patient-matched NF and UF were compared, without or with HAM extract. Studied parameters were proliferation rate, retraction of free-floating lattices, alpha smooth muscle actin expression by flow cytometry, and synthesis of elastin, glycosaminoglycans (GAGs), pro-collagen I, MMP-1 and TIMP-1. Our results show that UF had a specific phenotype compared to NF: low proliferation, high expression of alpha-SM actin and high synthesis of MMP-1, TIMP-1 and elastin. HAM extract significantly increased the synthesis of GAGs, pro-collagen I and MMP-1 in NF and decreased retraction of free lattices. HAM extract transiently increased UF proliferation, slowed down lattices retraction and decreased elastin synthesis. In conclusion, HAM extract has little effect on UF for the parameters studied and NF are more responsive than UF. However, clinical beneficial effect of HAM application on leg ulcers was previously observed and might rather be related to an action on keratinocytes and/or a modulation of the highly inflammatory environment of these chronic wounds.


Assuntos
Âmnio/metabolismo , Fibroblastos/citologia , Úlcera da Perna/terapia , Cicatrização/fisiologia , Âmnio/citologia , Terapia Baseada em Transplante de Células e Tecidos/métodos , Colágeno/metabolismo , Humanos , Fenótipo
6.
Am J Transplant ; 13(3): 656-62, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23331474

RESUMO

The natural history and clinical significance of posttransplant Epstein-Barr virus (EBV) infection remain largely unknown. The aims of this study are to describe the incidence, risk factors and consequences of EBV infection after kidney transplantation. A total of 383 consecutive patients having received a kidney transplant between January 2002 and December 2010 were included. EBV polymerase chain reaction (PCR) was performed every 2 weeks for 3 months, and every 4 weeks for the next 9 months. A total of 155 of the 383 patients (40%) had at least one positive viremia during the first year posttransplant. The median time to viremia was day 31 posttransplant (14-329). A total of 73 (47%) had EBV viremia > 10(3) log and 23 (15%) had positive viremia for more than 6 months. EBV D+/R- patients (12/18 (67%) versus 143/365 (39%), p = 0.02) and those having received antithymocyte globulins (ATG) (54% vs. 35%; p<0.001) were more likely to develop EBV infection. EBV infection (hazard ratio [HR], 3.03; 95% confidence interval [CI], 1.72-8.29; p = 0.01) was associated with the occurrence of opportunistic infections. A positive EBV PCR during the first 6 months posttransplant was associated with graft loss (HR, 3.04; 95% CI, 1.36-6.79; p = 0.014). EBV reactivation is frequent after transplantation and reflects overimmunosuppression. Prospective studies should examine the association between EBV and graft loss.


Assuntos
Infecções por Vírus Epstein-Barr/epidemiologia , Rejeição de Enxerto/epidemiologia , Sobrevivência de Enxerto , Nefropatias/virologia , Transplante de Rim/efeitos adversos , Viremia/epidemiologia , Adulto , DNA Viral/genética , Infecções por Vírus Epstein-Barr/diagnóstico , Infecções por Vírus Epstein-Barr/virologia , Feminino , França , Rejeição de Enxerto/diagnóstico , Rejeição de Enxerto/virologia , Herpesvirus Humano 4/isolamento & purificação , Humanos , Incidência , Nefropatias/terapia , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Fatores de Risco , Carga Viral , Viremia/diagnóstico , Viremia/virologia
7.
Arthritis Res Ther ; 24(1): 97, 2022 04 29.
Artigo em Inglês | MEDLINE | ID: mdl-35488311

RESUMO

AIM: This study explored the systemic vascular effects of local cryotherapy with a focus on endothelial changes and arterial inflammation in the model of rat adjuvant-induced arthritis (AIA). METHODS: Cryotherapy was applied twice a day on hind paws of AIA rats from the onset of arthritis to the acute inflammatory phase. Endothelial activation was studied in the aorta by measuring the mRNA levels of chemokines (CXCL-1, MCP-1 (CCL-2), MIP-1α (CCL-3)) and adhesion molecules (ICAM-1, VCAM-1) by qRT-PCR. Endothelial dysfunction was measured in isolated aortic and mesenteric rings. Aortic inflammation was evaluated via the mRNA expression of pro-inflammatory cytokines (TNF-α, IL-6) by qRT-PCR and leucocyte infiltration analysis (flow cytometry). Plasma levels of TNF-α, IL-6, IL-1ß, IL-17A, and osteoprotegerin (OPG) were measured using Multiplex/ELISA. RESULTS: AIA was associated with an increased aortic expression of CXCL-1 and ICAM-1 as well as an infiltration of leucocytes and increased mRNA expression of IL-6, IL-1ß, and TNF-α. Local cryotherapy, which decreased arthritis score and structural damages, reduced aortic mRNA expression of CXCL-1, IL-6, IL-1ß, and TNF-α, as well as aortic infiltration of leucocytes (T lymphocytes, monocytes/macrophages, neutrophils) and improved acetylcholine-induced vasorelaxation in the aorta and mesenteric arteries. Plasma levels of IL-17A and OPG were significantly reduced by cryotherapy, while the number of circulating leucocytes was not. IL-17A levels positively correlated with endothelial activation and dysfunction. CONCLUSION: In the AIA model, local cryotherapy reduced systemic endothelial activation, immune cell infiltration, and endothelial dysfunction. Mechanistically, the reduction of circulating levels of IL-17A appears as the possible link between joint cooling and the remote vascular effects.


Assuntos
Artrite Experimental , Molécula 1 de Adesão Intercelular , Animais , Crioterapia , Inflamação , Interleucina-17 , Interleucina-6 , RNA Mensageiro , Ratos , Ratos Endogâmicos Lew , Fator de Necrose Tumoral alfa
8.
Ann Dermatol Venereol ; 138(8-9): 572-9, 2011.
Artigo em Francês | MEDLINE | ID: mdl-21893230

RESUMO

BACKGROUND: The aim of our paper is to examine changes in the use of human amniotic membrane for venous leg ulcers through clinical studies and to present different models of tissue engineering employing human amniotic membrane for the purpose of future therapeutic use in wound healing. MATERIALS AND METHODS: This review is based on information obtained from a PubMed search using the following keywords "Amnion"[Mesh] AND "Leg Ulcer"[Mesh]; "Amnion"[Mesh] AND "Dermatology"[Mesh]. The selected articles are in English or French and deal with the sole use of human amniotic membrane in venous leg ulcers alone. RESULTS: Human amniotic membrane has a positive impact on chronic venous leg ulcers by promoting granulation tissue formation, reducing fibrosis and inducing re-epithelialisation. Nevertheless, further randomized clinical studies are needed. At the same time, tissue engineering models using human amniotic membrane may help to reduce wound healing time, thereby creating renewed interest in the use of human amniotic membrane. CONCLUSION: Considering its properties and the clinical studies analysed, human amniotic membrane could be useful in venous leg ulcer care.


Assuntos
Curativos Biológicos , Úlcera da Perna/terapia , Âmnio , Curativos Biológicos/tendências , Doença Crônica , Ensaios Clínicos como Assunto , Estudos de Coortes , Previsões , Tecido de Granulação/fisiologia , Humanos , Estudos Retrospectivos , Engenharia Tecidual/tendências , Preservação de Tecido/métodos , Cicatrização
9.
J Immunol Methods ; 483: 112810, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32592772

RESUMO

The ingestion of apoptotic corpses by macrophages, a process called efferocytosis, is a crucial step in inflammation resolution, since it alters macrophage phenotype toward a pro-resolving profile to foil inflammation and to favor tissue repair. Up to now, the resolving macrophages remain poorly characterized, especially in humans. Global investigations, like RNA sequencing, would be very helpful to unravel some features of these elusive cells. Nonetheless, these inquiries may be challenging in a single-species model, since the fate of ingested mRNA remains unknown and may hinder any subsequent mRNA investigations in the phagocyte. A full human model consisting of primary human neutrophil and primary human monocyte-derived macrophage co-culture was set up several decades ago to mimic in vitro the efferocytosis process. However, to our knowledge, this model has not been characterized as a suitable model to perform global mRNA investigations. Indeed, the extent of ingested neutrophil mRNA contamination has not been assessed in resolving macrophages. This work answers to this crucial question. Indeed, based on the protocols presented in this article, we demonstrate that neutrophil mRNA is severely degraded and is not able to cross-contaminate resolving macrophage mRNA, contrary to apoptotic human peripheral blood derived mononuclear cell (PBMC) or apoptotic leukemic Jurkat cell mRNA. Moreover, this allogenic co-culture system does not favor neither neutrophil activation nor macrophage pro-inflammatory cytokine release. Collectively, we highlight that this model of primary human neutrophil and primary human monocyte-derived macrophage co-culture is the best model for mRNA investigations in human resolving macrophages to help improving our knowledge on these crucial cells.


Assuntos
Macrófagos/metabolismo , Neutrófilos/metabolismo , Fagocitose , RNA Mensageiro/metabolismo , Apoptose , Células Cultivadas , Técnicas de Cocultura , Citocinas/genética , Citocinas/metabolismo , Humanos , Ativação de Macrófagos , Macrófagos/imunologia , Neutrófilos/imunologia , Neutrófilos/patologia , Cultura Primária de Células , Estabilidade de RNA , RNA Mensageiro/genética
10.
Am J Transplant ; 9(12): 2752-7, 2009 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-19788502

RESUMO

A G-->C polymorphism has been identified in the human cyclooxygenase-2 (COX-2) gene promoter at position -765 with C allele leading to a decreased promoter activity with low prostaglandin E2 (PGE2) production. PGE2 has strong immunomodulatory properties that could influence graft survival. We studied the association between this polymorphism and allograft failure in two independent cohorts of renal transplant recipients (RTRs) including a total of 603 patients. The functional effect of COX-2 gene promoter polymorphism was analyzed by measuring serum levels of PGE2. Median follow-up was 8.7 and 7.9 years for the first and second cohort, respectively. Analysis of 603 patients identified 20 CC (3.3%), 179 GC (29.7%) and 404 GG (67%) carriers. Patients with the GG genotype had significantly higher serum PGE2 concentrations than patients with the C allele. Carriers with a C allele have an independent increased risk of graft loss (hazard ratio (HR) 2.43 [95% CI 1.19-4.97], p = 0.015 for cohort 1; HR 1.72 [95% CI 0.99-3.77], p = 0.051 for cohort 2) compared to GG patients. COX-2 gene promoter polymorphism at position -765 (G-->C) is associated with a higher rate of graft loss in RTRs. Such findings may be used to influence immunosuppressive strategies and optimize patient management.


Assuntos
Ciclo-Oxigenase 2/genética , Transplante de Rim/efeitos adversos , Regiões Promotoras Genéticas , Adulto , Estudos de Coortes , Dinoprostona/sangue , Feminino , Rejeição de Enxerto/genética , Sobrevivência de Enxerto/genética , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo Genético
11.
Arthritis Res Ther ; 21(1): 180, 2019 07 30.
Artigo em Inglês | MEDLINE | ID: mdl-31362785

RESUMO

BACKGROUND: The aim of this study was to assess the anti-inflammatory effects of local cryotherapy in human non-septic knee arthritis. METHODS: In the phase I of the study, patients were randomized to receive either ice (30 min; N = 16) or cold CO2 (2 min; N = 16) applied twice during 1 day at an 8-h interval on the arthritic knee. In phase II, 16 other ice-treated arthritic knees according to the same protocol were compared to the contralateral non-treated arthritic knees (N = 16). The synovial fluid was analyzed just before the first cold application, then 24 h later. IL-6, IL-1ß, TNF-α, IL-17A, VEGF, NF-kB-p65 protein, and PG-E2 levels were measured in the synovial fluid and compared before/after the two cold applications. RESULTS: Forty-seven patients were included (17 gouts, 11 calcium pyrophosphate deposition diseases, 13 rheumatoid arthritides, 6 spondyloarthritides). Local ice cryotherapy significantly reduced the IL-6, IL-1ß, VEGF, NF-kB-p65, and PG-E2 synovial levels, especially in the microcrystal-induced arthritis subgroup, while only phosphorylated NF-kB-p65 significantly decreased in rheumatoid arthritis and spondyloarthritis patients. Cold CO2 only reduced the synovial VEGF levels. In the phase II of the study, the synovial PG-E2 was significantly reduced in ice-treated knees, while it significantly increased in the corresponding contralateral non-treated arthritic knees, with a significant inter-class effect size (mean difference - 1329 [- 2232; - 426] pg/mL; N = 12). CONCLUSIONS: These results suggest that local ice cryotherapy reduces IL-6, IL-1ß, and VEGF synovial protein levels, mainly in microcrystal-induced arthritis, and potentially through NF-kB and PG-E2-dependent mechanisms. TRIAL REGISTRATION: Clinicaltrials.gov, NCT03850392-registered February 20, 2019-retrospectively registered.


Assuntos
Crioterapia/métodos , Interleucina-1beta/metabolismo , Interleucina-6/metabolismo , NF-kappa B/metabolismo , Osteoartrite do Joelho/terapia , Fator A de Crescimento do Endotélio Vascular/metabolismo , Adulto , Idoso , Biomarcadores/metabolismo , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Osteoartrite do Joelho/diagnóstico , Osteoartrite do Joelho/metabolismo , Líquido Sinovial/metabolismo , Resultado do Tratamento
12.
Transfus Clin Biol ; 15(3): 98-108, 2008 Jun.
Artigo em Francês | MEDLINE | ID: mdl-18524660

RESUMO

In the past few years, significant advances have been performed in the field of cell-based therapies. This concerns mainly regenerative medicine with the use of stem cells, as well as the modulation of immune responses. In order to modulate allogeneic immune responses after transplantation, we have developed a cell therapy approach based on the immunomodulatory properties of intravenous donor apoptotic cell infusion. In allogeneic hematopoietic cell transplantation settings, we reported that intravenous apoptotic leukocyte infusion, simultaneously to allogeneic bone marrow grafts, favors hematopoietic engraftment, prevents alloimmunization and delays graft-versus-host disease. Here, we review the different factors and cells implicated in the immunomodulatory properties of apoptotic cells. Then, we discuss the potential significance of such observations in transfusion practice.


Assuntos
Apoptose , Transfusão de Leucócitos , Leucócitos/imunologia , Transfusão de Sangue , Transplante de Medula Óssea/métodos , Citocinas/fisiologia , Doença Enxerto-Hospedeiro/prevenção & controle , Transplante de Células-Tronco Hematopoéticas/métodos , Humanos , Terapia de Imunossupressão/métodos , Infusões Intravenosas , Leucócitos/citologia , Transplante Homólogo/efeitos adversos
13.
Ann Pharm Fr ; 66(2): 115-21, 2008 Mar.
Artigo em Francês | MEDLINE | ID: mdl-18570910

RESUMO

While the use of nonspecific immunosuppressive drugs has significantly reduced the incidence of acute graft rejection, the benefits of such therapies on chronic rejection and overall long-term graft survival are uncertain. Persistent excessive immunosuppression after immunosuppressive drug treatment is associated with long-term toxicity including increased incidence of cancers, severe infectious complications and metabolic diseases (for example, diabetes, atherosclerosis). One of our team's aims is to identify immunological factors that can predict such toxicities. We have previously demonstrated that CD4T cell cytopenia was correlated with high risk of cancers and infections as well as atherosclerosis in renal transplant recipients. Now, we are investigating the mechanisms involved in CD4T cell cytopenia. We are also exploring how inflammation and cells from the innate immunity influence the complications associated with kidney transplantation. This was performed through the analysis of gene polymorphism on TLR-4, NOD2/CARD15 receptors and IL-6 promoter and correlation with transplantation outcome. We already correlated IL-6 promoter gene polymorphism at position -174 with new-onset diabetes after transplantation in overweight patients. Identification of gene polymorphisms or factors associated with complications after transplantation may help physicians to determine high-risk recipient profiles and optimize pre- and post-transplantation treatment strategies.


Assuntos
Imunossupressores/efeitos adversos , Transplante de Rim/imunologia , Monitoramento de Medicamentos , Rejeição de Enxerto/prevenção & controle , Humanos , Imunossupressores/administração & dosagem , Imunossupressores/uso terapêutico
14.
Int Rev Immunol ; 37(4): 183-191, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30081695

RESUMO

T cell depletion by polyclonal antithymocyte globulins (ATG) has been used for many years in both organ and hematopoietic cell transplantation as an induction and rejection therapy. Nevertheless, its use remains largely empirical and many clinical questions, such as the determination of an individualized dose, therapeutic relevance of nondepletive effects, or prediction of long-term effects, are still unresolved. This review evaluates the evidence-based knowledge and the uncertainties concerning ATG, and suggests perspectives and opportunities for modern use of this old drug.


Assuntos
Soro Antilinfocitário/uso terapêutico , Rejeição de Enxerto/prevenção & controle , Imunossupressores/uso terapêutico , Transplante de Rim/efeitos adversos , Depleção Linfocítica/métodos , Soro Antilinfocitário/farmacologia , Uso de Medicamentos/normas , Uso de Medicamentos/tendências , Medicina Baseada em Evidências/métodos , Rejeição de Enxerto/imunologia , Humanos , Imunossupressores/farmacologia , Depleção Linfocítica/normas , Guias de Prática Clínica como Assunto , Medição de Risco , Linfócitos T/efeitos dos fármacos , Linfócitos T/imunologia
15.
Cell Death Differ ; 13(1): 41-52, 2006 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-15962005

RESUMO

Apoptotic leukocytes are endowed with immunomodulatory properties that can be used to enhance hematopoietic engraftment and prevent graft-versus-host disease (GvHD). This apoptotic cell-induced tolerogenic effect is mediated by host macrophages and not recipient dendritic cells or donor phagocytes present in the bone marrow graft as evidenced by selective cell depletion and trafficking experiments. Furthermore, apoptotic cell infusion is associated with TGF-beta-dependent donor CD4+CD25+ T-cell expansion. Such cells have a regulatory phenotype (CD62L(high) and intracellular CTLA-4+), express high levels of forkhead-box transcription factor p3 (Foxp3) mRNA and exert ex vivo suppressive activity through a cell-to-cell contact mechanism. In vivo CD25 depletion after apoptotic cell infusion prevents the apoptotic cell-induced beneficial effects on engraftment and GvHD occurrence. This highlights the role of regulatory T cells in the tolerogenic effect of apoptotic cell infusion. This novel association between apoptosis and regulatory T-cell expansion may also contribute to preventing deleterious autoimmune responses during normal turnover.


Assuntos
Apoptose/imunologia , Baço/citologia , Baço/imunologia , Linfócitos T Reguladores/imunologia , Fator de Crescimento Transformador beta/metabolismo , Transferência Adotiva , Animais , Transplante de Medula Óssea/imunologia , Células Dendríticas/imunologia , Fatores de Transcrição Forkhead/genética , Sobrevivência de Enxerto/imunologia , Doença Enxerto-Hospedeiro/prevenção & controle , Tolerância Imunológica , Técnicas In Vitro , Macrófagos/imunologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , RNA Mensageiro/genética , Receptores de Interleucina-2/metabolismo
16.
J Clin Invest ; 99(6): 1173-8, 1997 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-9077524

RESUMO

Astrocytomas are among the most common brain tumors that are usually fatal in their malignant form. They appear to progress without significant impedance from the immune system, despite the presence of intratumoral T cell infiltration. To date, this has been thought to be the result of T cell immunosuppression induced by astrocytoma-derived cytokines. Here, we propose that cell contact-mediated events also play a role, since we demonstrate the in vivo expression of Fas ligand (FasL/CD95L) by human astrocytoma and the efficient killing of Fas-bearing cells by astrocytoma lines in vitro and by tumor cells ex vivo. Functional FasL is expressed by human, mouse, and rat astrocytoma and hence may be a general feature of this nonlymphoid tumor. In the brain, astrocytoma cells can potentially deliver a death signal to Fas+ cells which include infiltrating leukocytes and, paradoxically, astrocytoma cells themselves. The expression of FasL by astrocytoma cells may extend the processes that are postulated to occur in normal brain to maintain immune privilege, since we also show FasL expression by neurons. Overall, our findings suggest that FasL-induced apoptosis by astrocytoma cells may play a significant role in both immunosuppression and the regulation of tumor growth within the central nervous system.


Assuntos
Astrocitoma/imunologia , Neoplasias Encefálicas/imunologia , Encéfalo/imunologia , Glicoproteínas de Membrana/biossíntese , Receptor fas/metabolismo , Animais , Astrocitoma/metabolismo , Astrocitoma/patologia , Encéfalo/metabolismo , Encéfalo/patologia , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/patologia , Testes Imunológicos de Citotoxicidade , Proteína Ligante Fas , Humanos , Ligantes , Glicoproteínas de Membrana/fisiologia , Camundongos , Ratos , Células Tumorais Cultivadas
17.
Curr Opin Immunol ; 10(5): 564-72, 1998 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-9794830

RESUMO

Tumors of diverse origin have recently been shown to express CD95 ligand and to induce apoptosis in CD95-expressing targets in vitro; however, in vivo, enhanced tumor growth and rejection have both been observed as a consequence of either immunosuppressive or proinflammatory functions of CD95 ligand. The final in vivo outcome of CD95 ligand expression will depend upon a complex balance of interactions relevant for each tumor in its particular microenvironment.


Assuntos
Glicoproteínas de Membrana/fisiologia , Neoplasias/imunologia , Animais , Proteína Ligante Fas , Humanos , Glicoproteínas de Membrana/análise , Neoplasias/patologia , Linfócitos T/imunologia
18.
Mucosal Immunol ; 9(2): 309-21, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26153763

RESUMO

Acute graft-versus-host disease (aGVHD) remains a major complication following allogeneic hematopoietic cell transplantation, limiting the success of this therapy. We previously reported that interleukin-22 (IL-22) participates to aGVHD development, but the underlying mechanisms of its contribution remain poorly understood. In this study, we analyzed the mechanism of the pathological function of IL-22 in intestinal aGVHD. Ex-vivo colon culture experiments indicated that IL-22 was able to induce Th1-like inflammation via signal transducer and activator of transcription factor-1 (STAT1) and CXCL10 induction in the presence of type I interferon (IFN). To evaluate a potential synergy between IL-22 and type I IFN in aGVHD, we transplanted recipient mice, either wild-type (WT) or type I IFN receptor deficient (IFNAR(-/-)), with bone marrow cells and WT or IL-22 deficient (IL-22(-/-)) T cells. We observed a decreased GVHD severity in IFNAR(-/-) recipient of IL-22(-/-) T cells, which was associated with a lower level of STAT1 activation and reduced CXCL10 expression in the large intestine. Finally, immunohistochemistry staining of STAT1 performed on gastrointestinal biopsies of 20 transplanted patients showed exacerbated STAT1 activation in gastrointestinal tissues of patients with aGVHD as compared with those without aGVHD. Thus, interfering with both IL-22 and type I IFN signaling may provide a novel approach to limit aGVHD.


Assuntos
Transplante de Medula Óssea , Quimiocina CXCL10/imunologia , Doença Enxerto-Hospedeiro/imunologia , Interferon Tipo I/imunologia , Interleucinas/imunologia , Intestino Grosso/imunologia , Fator de Transcrição STAT1/imunologia , Animais , Medula Óssea/imunologia , Medula Óssea/patologia , Quimiocina CXCL10/genética , Regulação da Expressão Gênica , Doença Enxerto-Hospedeiro/genética , Doença Enxerto-Hospedeiro/patologia , Neoplasias Hematológicas/genética , Neoplasias Hematológicas/imunologia , Neoplasias Hematológicas/patologia , Neoplasias Hematológicas/terapia , Humanos , Interferon Tipo I/genética , Interleucinas/deficiência , Interleucinas/genética , Mucosa Intestinal/imunologia , Mucosa Intestinal/patologia , Intestino Grosso/patologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Camundongos Knockout , Receptor de Interferon alfa e beta/deficiência , Receptor de Interferon alfa e beta/genética , Receptor de Interferon alfa e beta/imunologia , Fator de Transcrição STAT1/genética , Transdução de Sinais , Células Th1/imunologia , Células Th1/patologia , Doadores de Tecidos , Transplante Homólogo , Irradiação Corporal Total , Interleucina 22
19.
Bone Marrow Transplant ; 35(9): 859-68, 2005 May.
Artigo em Inglês | MEDLINE | ID: mdl-15765116

RESUMO

Peripheral blood stem cell transplantation after reduced-intensity conditioning (RIC-PBSCT) regimen is an alternative to conventional regimens with less immediate toxicity. Since immune recovery is of crucial importance for the control of infections, we retrospectively studied the recovery of T-, B- and NK cell subsets in 20 consecutive patients undergoing RIC-PBSCT. We also studied the thymic output using T-cell receptor excision circle assay. Engraftment was rapid and few infectious complications were seen: three early (before 2.5 months) cases of asymptomatic cytomegalovirus reactivation, two late Gram-negative bacterial infections and no fungal infection. While CD4+ T-cell reconstitution was slow, CD8+ T-cell counts were close to normal values at 4 months. Median CD19+ B-cell counts reached normal values at 11 months. Rapid CD56+ NK cell reconstitution was noticed as early as 1.5 months. Low T-cell receptor excision circle numbers and preponderance of memory-type subsets among T cells further suggested that CD8+ T-cell reconstitution resulted predominantly from peripheral expansion and that thymic-dependent reconstitution was severely impaired. In conclusion, large peripheral T-cell expansion may compensate for late thymic-dependent lymphopoiesis, and may, with other factors such as NK and B-cell reconstitution and careful antiinfectious prophylaxis, help limit the incidence of severe infections after RIC-PBSCT.


Assuntos
Infecções por Citomegalovirus , Infecções por Bactérias Gram-Negativas , Subpopulações de Linfócitos/imunologia , Transplante de Células-Tronco de Sangue Periférico , Recuperação de Função Fisiológica/imunologia , Condicionamento Pré-Transplante , Adulto , Idoso , Linfócitos B , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , Infecções por Citomegalovirus/imunologia , Infecções por Citomegalovirus/virologia , Feminino , Infecções por Bactérias Gram-Negativas/imunologia , Infecções por Bactérias Gram-Negativas/microbiologia , Humanos , Células Matadoras Naturais/imunologia , Masculino , Pessoa de Meia-Idade , Condicionamento Pré-Transplante/métodos , Transplante Homólogo
20.
Exp Hematol ; 29(6): 736-45, 2001 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-11378269

RESUMO

OBJECTIVE: The hematopoietic microenvironment is complex, and the role of myofibroblast in its function is crucial. In order to obtain a stable model reflecting this particular cell type, we have previously established human bone marrow cell lines from primary myofibroblastic Stro1(+) population (pStro1(+)). We placed HPV16 E6 and E7 expression under the control of different promoters. Here, we have characterized and studied the hematopoietic support for two cell lines corresponding to the promoters alpha-SM (alphaSM-56 line) and SV40 (SV40-56 line). MATERIALS AND METHODS: The expression profile was analyzed at the RNA level by gene array and at the protein level by Western blot, flow cytometry, and ELISA. Hematopoietic support determined using colony-forming unit (CFU) and stroma-adherent colony-forming cell (SA-CFC) assays. RESULTS: The phenotype of cell lines was not significantly modified compared with primary myofibroblastic cells. They secreted a broad spectrum of hematopoietic cytokines and nonspecific mediators. The two lines allowed the growth of hematopoietic precursors and had different support capabilities. CONCLUSIONS: We have extensively characterized two novel human bone marrow stromal cell lines. They retained a myofibroblastic phenotype and have substantial but different hematopoietic support capabilities. These lines provided a basis for determining stromal factors involved in stem-cell regulation.


Assuntos
Citocinas/genética , Células-Tronco Hematopoéticas/fisiologia , Células Estromais/fisiologia , Antígenos CD34/análise , Células da Medula Óssea/citologia , Adesão Celular , Moléculas de Adesão Celular/análise , Linhagem Celular , Células Cultivadas , Técnicas de Cocultura , Ensaio de Unidades Formadoras de Colônias , Criopreservação , Meios de Cultura , Citocinas/análise , Citometria de Fluxo , Células-Tronco Hematopoéticas/citologia , Humanos , Integrinas/análise , Fenótipo , Células Estromais/citologia
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA