Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 15 de 15
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Cells ; 9(1)2020 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-31947623

RESUMO

Androgen receptor (AR) signaling remains crucial in castration-resistant prostate cancer (CRPC). Since it is also essential in immune cells, we studied whether the expression of AR full-length (ARFL) and its splicing variant ARV7 in peripheral blood mononuclear cells (PBMC) predicts systemic treatment response in mCRPC in comparison with circulating-tumor cells (CTC). We measured ARFL and ARV7 mRNA in PBMC and CTC from patients prior to receiving abiraterone (AA), enzalutamide (E), or taxanes by a pre-amplification plus quantitative reverse-transcription PCR. They were also tested in LNCaP-ARV7-transfected and in 22RV1 docetaxel-resistant (22RV1DR) cells. We studied 171 PBMC from 136 patients and from 24 non-cancer controls, and 47 CTC from 22 patients. High PBMC ARV7 levels correlated with worse AA/E and better taxane response. In taxane-treated patients high PBMC ARFL also correlated with longer progression-free survival (PFS). High ARV7 and ARFL expression were independently associated with better biochemical-PFS. Conversely, high CTC ARV7 and ARFL correlated with shorter radiological-PFS and overall survival, respectively. High ARV7 in 22RV1DR and LNCaP-ARV7 cells correlated with taxane resistance. In conclusion, ARFL and ARV7 at PBMC or CTC have a different predictive role in the taxane response, suggesting a potential influence of the AR pathway from PBMC in such response modulation.

2.
Proc Natl Acad Sci U S A ; 116(17): 8463-8470, 2019 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-30962374

RESUMO

There are adaptive T-cell and antibody autoimmune responses to myelin-derived peptides in multiple sclerosis (MS) and to aquaporin-4 (AQP4) in neuromyelitis optica spectrum disorders (NMOSDs). Strategies aimed at antigen-specific tolerance to these autoantigens are thus indicated for these diseases. One approach involves induction of tolerance with engineered dendritic cells (tolDCs) loaded with specific antigens. We conducted an in-human phase 1b clinical trial testing increasing concentrations of autologous tolDCs loaded with peptides from various myelin proteins and from AQP4. We tested this approach in 12 patients, 8 with MS and 4 with NMOSD. The primary end point was the safety and tolerability, while secondary end points were clinical outcomes (relapses and disability), imaging (MRI and optical coherence tomography), and immunological responses. Therapy with tolDCs was well tolerated, without serious adverse events and with no therapy-related reactions. Patients remained stable clinically in terms of relapse, disability, and in various measurements using imaging. We observed a significant increase in the production of IL-10 levels in PBMCs stimulated with the peptides as well as an increase in the frequency of a regulatory T cell, known as Tr1, by week 12 of follow-up. In this phase 1b trial, we concluded that the i.v. administration of peptide-loaded dendritic cells is safe and feasible. Elicitation of specific IL-10 production by peptide-specific T cells in MS and NMOSD patients indicates that a key element in antigen specific tolerance is activated with this approach. The results warrant further clinical testing in larger trials.

3.
Front Immunol ; 9: 1169, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29904379

RESUMO

The identification of activated T-lymphocytes restricted to myelin-derived immunogenic peptides in multiple sclerosis (MS) and aquaporin-4 water channel in neuromyelitis optica (NMO) in the blood of patients opened the possibility for developing highly selective and disease-specific therapeutic approaches. Antigen presenting cells and in particular dendritic cells (DCs) represent a strategy to inhibit pro-inflammatory T helper cells. DCs are located in peripheral and lymphoid tissues and are essential for homeostasis of T cell-dependent immune responses. The expression of a particular set of receptors involved in pathogen recognition confers to DCs the property to initiate immune responses. However, in the absence of danger signals different DC subsets have been revealed to induce active tolerance by inducing regulatory T cells, inhibiting pro-inflammatory T helper cells responses or both. Interestingly, several protocols to generate clinical-grade tolerogenic DC (Tol-DC) in vitro have been described, offering the possibility to restore the homeostasis to central nervous system-related antigens. In this review, we discuss about different DC subsets and their role in tolerance induction, the different protocols to generate Tol-DCs and preclinical studies in animal models as well as describe recent characterization of Tol-DCs for clinical application in autoimmune diseases and in particular in MS and NMO patients. In addition, we discuss the clinical trials ongoing based on Tol-DCs to treat different autoimmune diseases.


Assuntos
Células Dendríticas/imunologia , Imunoterapia/métodos , Esclerose Múltipla/terapia , Neuromielite Óptica/terapia , Linfócitos T Auxiliares-Indutores/imunologia , Alarminas/metabolismo , Animais , Apresentação do Antígeno , Aquaporina 4/imunologia , Autoantígenos/imunologia , Células Dendríticas/transplante , Humanos , Tolerância Imunológica , Imunoterapia/tendências , Ativação Linfocitária , Bainha de Mielina/imunologia , Especificidade do Receptor de Antígeno de Linfócitos T
5.
Front Oncol ; 8: 127, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29755954

RESUMO

Background and objective: Diffuse intrinsic pontine glioma (DIPG) is a lethal brainstem tumor in children. Dendritic cells (DCs) have T-cell stimulatory capacity and, therefore, potential antitumor activity for disease control. DCs vaccines have been shown to reactivate tumor-specific T cells in both clinical and preclinical settings. We designed a phase Ib immunotherapy (IT) clinical trial with the use of autologous dendritic cells (ADCs) pulsed with an allogeneic tumors cell-lines lysate in patients with newly diagnosed DIPG after irradiation (radiation therapy). Methods: Nine patients with newly diagnosed DIPG met enrollment criteria. Autologous dendritic cell vaccines (ADCV) were prepared from monocytes obtained by leukapheresis. Five ADCV doses were administered intradermally during induction phase. In the absence of tumor progression, patients received three boosts of tumor lysate every 3 months during the maintenance phase. Results: Vaccine fabrication was feasible in all patients included in the study. Non-specific KLH (9/9 patients) and specific (8/9 patients) antitumor response was identified by immunologic studies in peripheral blood mononuclear cells (PBMC). Immunological responses were also confirmed in the T lymphocytes isolated from the cerebrospinal fluid (CSF) of two patients. Vaccine administration resulted safe in all patients treated with this schema. Conclusion: These preliminary results demonstrate that ADCV preparation is feasible, safe, and generate a DIPG-specific immune response detected in PBMC and CSF. This strategy shows a promising backbone for future schemas of combination IT.

6.
J Leukoc Biol ; 102(3): 881-895, 2017 09.
Artigo em Inglês | MEDLINE | ID: mdl-28630103

RESUMO

Dendritic cells (DCs) are APCs essential in regulating the immune response. PGE2, produced during inflammation, has a pivotal role in the maturation of DCs and, therefore, is vital for the immune response. The large variety of biologic functions governed by PGE2 is mediated by its signaling through 4 distinct E-type prostanoid (EP) receptors. Immunogenic DCs express EP2 and EP4, which mediate the PGE2 signaling. However, the expression and function of EP receptors in human tolerogenic DCs (tol-DCs), which present an inhibitory phenotype, have not yet, to our knowledge, been assessed. To clarify the role of EP receptors in tol-DCs, we examined the expression of different EP receptors and their effect using selective agonists in human cells. We find that EP2 and EP3 expression are up-regulated in in vitro-generated tol-DCs compared with mature DCs (mDCs). Activation of EP2-EP4 has a direct effect on the surface expression of costimulatory molecules and maturation receptors, such as CD80, CD83, and CD86 or MHCII and CCR7 in tol-DCs, the latter being exclusively modulated by PGE2-EP4 signaling. Importantly, we find that EP2 and EP3 receptors are involved in tolerance induction through IL-10 production by tol-DCs. These results are in sharp contrast with the inflammatory role of EP4 Moreover, we show that DCs generated in the presence of agonists for EP receptors, induce naive T cell differentiation toward polarized Th1/Th17 cells. Given the differential effects of EP receptors, our results suggest that EP receptor agonist/antagonists might become relevant novel drug templates to modulate immune response.


Assuntos
Células Dendríticas/imunologia , Dinoprostona/farmacologia , Tolerância Imunológica/efeitos dos fármacos , Imunossupressores/farmacologia , Receptores de Prostaglandina E Subtipo EP2/imunologia , Receptores de Prostaglandina E Subtipo EP3/imunologia , Antígenos CD/imunologia , Antígenos de Histocompatibilidade Classe II/imunologia , Humanos , Interleucina-10/imunologia , Receptores CCR7/imunologia , Células Th1/imunologia , Células Th17/imunologia
7.
Int J Pharm ; 511(2): 785-93, 2016 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-27477102

RESUMO

The design of innovative strategies to selectively target cells, such antigen-presenting cells and dendritic cells, in vivo to induce immune tolerance is gaining interest and relevance for the treatment of immune-mediated diseases. A novel loaded-nanosystem strategy to generate tolerogenic dendritic cells (tol-DCs) was evaluated. Hence budesonide (BDS) was encapsulated in multiwalled polyurethane-polyurea nanoparticles (PUUa NPs-BDS) based on self-stratified polymers by hydrophobic interactions at the oil-water interface. DCs treated with encapsulated BDS presented a prominent downregulation of costimulatory molecules (CD80, CD83 and MHCII) and upregulation of inhibitory receptors. Moreover, DCs treated with these PUUa NPs-BDS also secreted large amounts of IL-10, a crucial anti-inflammatory cytokine to induce tolerance, and inhibited T lymphocyte activation in a specific manner compared to those cells generated with free BDS. These results demonstrate that PUUa NPs-BDS are a highly specific and efficient system through which to induce DCs with a tolerogenic profile. Given the capacity of PUUa NPs-BDS, this delivery system has a clear advantage for translation to in vivo studies.


Assuntos
Budesonida/farmacologia , Células Dendríticas/imunologia , Tolerância Imunológica/efeitos dos fármacos , Nanopartículas/química , Polímeros/química , Poliuretanos/química , Antígenos CD/metabolismo , Antígeno B7-1/metabolismo , Budesonida/química , Proliferação de Células/efeitos dos fármacos , Citocinas/metabolismo , Humanos , Imunoglobulinas/metabolismo , Interleucina-10/metabolismo , Ativação Linfocitária/efeitos dos fármacos , Glicoproteínas de Membrana/metabolismo , Nanopartículas/ultraestrutura , Proteínas Nucleares/metabolismo , Tamanho da Partícula , Linfócitos T/efeitos dos fármacos , Transativadores/metabolismo
8.
Clin Transl Immunology ; 5(1): e61, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26900474

RESUMO

HLDA10 is the Tenth Human Leukocyte Differentiation Antigen (HLDA) Workshop. The HLDA Workshops provide a mechanism to allocate cluster of differentiation (CD) nomenclature by engaging in interlaboratory studies. As the host laboratory, we invited researchers from national and international academic and commercial institutions to submit monoclonal antibodies (mAbs) to human leukocyte surface membrane molecules, particularly those that recognised molecules on human myeloid cell populations and dendritic cells (DCs). These mAbs were tested for activity and then distributed as a blinded panel to 15 international laboratories to test on different leukocyte populations. These populations included blood DCs, skin-derived DCs, tonsil leukocytes, monocyte-derived DCs, CD34-derived DCs, macrophage populations and diagnostic acute myeloid leukaemia and lymphoma samples. Each laboratory was provided with enough mAb to perform five repeat experiments. Here, we summarise the reactivity of different mAb to 68 different cell-surface molecules expressed by human myeloid and DC populations. Submitted mAbs to some of the molecules were further validated to collate data required to designate a formal CD number. This collaborative process provides the broader scientific community with an invaluable data set validating mAbs to leukocyte-surface molecules.

9.
J Crohns Colitis ; 9(12): 1071-8, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26303633

RESUMO

BACKGROUND AND AIMS: Ex vivo-generated autologous tolerogenic dendritic cells [tolDCs] can restore immune tolerance in experimental colitis. The aim of this study was to determine the safety and tolerability of administration of autologous tolDCs in refractory Crohn's disease [CD] patients. METHODS: A phase-I, single-centre, sequential-cohorts, dose-range study was designed. Stable tolDCs were generated ex vivo from monocytes following a previously developed protocol, and administered by sonography-guided intraperitoneal injection. Six sequential refractory-CD cohorts were established: the first three cohorts received a single intraperitoneal injection of tolDCs at escalating doses [2 x 10(6)/5 x 10(6)/10 x 10(6)]; and the last three cohorts received three biweekly intraperitoneal injections at same escalating doses. Safety was sequentially evaluated. Patients were assessed from week 0 to 12 and followed up for 1-year period for safety. RESULTS: Nine patients were included. No adverse effects were detected during tolDC injection or follow-up. Three patients withdrew from the study due to CD worsening. Crohn's Disease Activity Index [CDAI] decreased from 274 [60] {mean (standard deviation [SD])} to 222 [113] [p = 0.3]; one [11%] patient reached clinical remission [CDAI < 150] and two [22%] clinical response [CDAI decrease ≥ 100]. Crohn's Disease Endoscopic Index of Severity [CDEIS] decreased from 18 [5] to 13 [8] [p = 0.4]; lesions improved markedly in three patients [33%]. Quality of life (inflammatory bowel disease questionnaire [IBDQ]) changed from 125 [27] to 131 [38] [p = 0.7]; remission [IBDQ at Week 12 ≥ 170] was reached in one [11%] case and response [IBDQ score increase ≥ 16] in two [22%]. CONCLUSIONS: Intraperitoneal administration of autologous tolDCs appears safe and feasible in refractory CD patients. Further studies should be developed to test clinical benefit, determine the optimal administration route and dose, and monitor the immune responses; See [www.eudract.ema.europa.eu, EudraCT number 2007-003469-42; www.aemps.gob.es number PEI 08-049].


Assuntos
Doença de Crohn/terapia , Células Dendríticas/transplante , Adolescente , Adulto , Idoso , Doença de Crohn/imunologia , Feminino , Seguimentos , Humanos , Injeções Intraperitoneais , Masculino , Pessoa de Meia-Idade , Transplante Autólogo , Resultado do Tratamento , Adulto Jovem
10.
J Leukoc Biol ; 97(4): 751-60, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25624460

RESUMO

The aim of this study was to test the hypothesis whether MERTK, which is up-regulated in human DCs treated with immunosuppressive agents, is directly involved in modulating T cell activation. MERTK is a member of the TAM family and contributes to regulating innate immune response to ACs by inhibiting DC activation in animal models. However, whether MERTK interacts directly with T cells has not been addressed. Here, we show that MERTK is highly expressed on dex-induced human tol-DCs and participates in their tolerogenic effect. Neutralization of MERTK in allogenic MLR, as well as autologous DC-T cell cultures, leads to increased T cell proliferation and IFN-γ production. Additionally, we identify a previously unrecognized noncell-autonomous regulatory function of MERTK expressed on DCs. Mer-Fc protein, used to mimic MERTK on DCs, suppresses naïve and antigen-specific memory T cell activation. This mechanism is mediated by the neutralization of the MERTK ligand PROS1. We find that MERTK and PROS1 are expressed in human T cells upon TCR activation and drive an autocrine proproliferative mechanism. Collectively, these results suggest that MERTK on DCs controls T cell activation and expansion through the competition for PROS1 interaction with MERTK in the T cells. In conclusion, this report identified MERTK as a potent suppressor of T cell response.


Assuntos
Linfócitos T CD4-Positivos/enzimologia , Células Dendríticas/enzimologia , Tolerância Imunológica/fisiologia , Ativação Linfocitária/fisiologia , Proteínas Proto-Oncogênicas/fisiologia , Receptores Proteína Tirosina Quinases/fisiologia , Antígenos de Bactérias/imunologia , Comunicação Autócrina , Proteínas Sanguíneas/fisiologia , Linfócitos T CD4-Positivos/citologia , Diferenciação Celular , Divisão Celular , Células Cultivadas , Técnicas de Cocultura , Células Dendríticas/efeitos dos fármacos , Células Dendríticas/imunologia , Dexametasona/farmacologia , Indução Enzimática/efeitos dos fármacos , Humanos , Memória Imunológica , Testes de Liberação de Interferon-gama , Teste de Cultura Mista de Linfócitos , Monócitos/citologia , Especificidade do Receptor de Antígeno de Linfócitos T , Regulação para Cima/efeitos dos fármacos , c-Mer Tirosina Quinase
11.
Mol Immunol ; 63(2): 343-54, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25282042

RESUMO

Cellular therapies using immune cells and in particular dendritic cells (DCs) are being increasingly applied in clinical trials and vaccines. Their success partially depends on accurate delivery of cells to target organs or migration to lymph nodes. Delivery and subsequent migration of cells to regional lymph nodes is essential for effective stimulation of the immune system. Thus, the design of an optimal DC therapy would be improved by optimizing technologies for monitoring DC trafficking. Magnetic resonance imaging (MRI) represents a powerful tool for non-invasive imaging of DC migration in vivo. Domestic pigs share similarities with humans and represent an excellent animal model for immunological studies. The aim of this study was to investigate the possibility using pigs as models for DC tracking in vivo. Porcine monocyte derived DC (MoDC) culture with superparamagnetic iron oxide (SPIO) particles was standardized on the basis of SPIO concentration and culture viability. Phenotype, cytokine production and mixed lymphocyte reaction assay confirmed that porcine SPIO-MoDC culture were similar to mock MoDCs and fully functional in vivo. Alike, similar patterns were obtained in human MoDCs. After subcutaneous inoculation in pigs, porcine SPIO-MoDC migration to regional lymph nodes was detected by MRI and confirmed by Perls staining of draining lymph nodes. Moreover, after one dose of virus-like particles-pulsed MoDCs specific local and systemic responses were confirmed using ELISPOT IFN-γ in pigs. In summary, the results in this work showed that after one single subcutaneous dose of pulsed MoDCs, pigs were able to elicit specific local and systemic immune responses. Additionally, the dynamic imaging of MRI-based DC tracking was shown using SPIO particles. This proof-of-principle study shows the potential of using pigs as a suitable animal model to test DC trafficking with the aim of improving cellular therapies.


Assuntos
Rastreamento de Células/métodos , Células Dendríticas/imunologia , Monócitos/citologia , Animais , Forma Celular , Sobrevivência Celular , Células Dendríticas/citologia , Dextranos/metabolismo , ELISPOT , Humanos , Imunização , Imuno-Histoquímica , Interferon gama/metabolismo , Linfonodos/patologia , Imagem por Ressonância Magnética , Nanopartículas de Magnetita , Fenótipo , Coloração e Rotulagem , Sus scrofa
12.
PLoS One ; 9(6): e99589, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24945611

RESUMO

LFA-1 is a leukocyte specific ß2 integrin that plays a major role in regulating adhesion and migration of different immune cells. Recent data suggest that LFA-1 on mature dendritic cells (mDCs) may function as a chemokine-inducible anchor during homing of DCs through the afferent lymphatics into the lymph nodes, by transiently switching its molecular conformational state. However, the role of LFA-1 mobility in this process is not yet known, despite that the importance of lateral organization and dynamics for LFA-1-mediated adhesion regulation is broadly recognized. Using single particle tracking approaches we here show that LFA-1 exhibits higher mobility on resting mDCs compared to monocytes. Lymphoid chemokine CCL21 stimulation of the LFA-1 high affinity state on mDCs, led to a significant reduction of mobility and an increase on the fraction of stationary receptors, consistent with re-activation of the receptor. Addition of soluble monomeric ICAM-1 in the presence of CCL21 did not alter the diffusion profile of LFA-1 while soluble ICAM-1 nano-aggregates in the presence of CCL21 further reduced LFA-1 mobility and readily bound to the receptor. Overall, our results emphasize the importance of LFA-1 lateral mobility across the membrane on the regulation of integrin activation and its function as adhesion receptor. Importantly, our data show that chemokines alone are not sufficient to trigger the high affinity state of the integrin based on the strict definition that affinity refers to the adhesion capacity of a single receptor to its ligand in solution. Instead our data indicate that nanoclustering of the receptor, induced by multi-ligand binding, is required to maintain stable cell adhesion once LFA-1 high affinity state is transiently triggered by inside-out signals.


Assuntos
Quimiocina CCL21/metabolismo , Células Dendríticas/metabolismo , Molécula 1 de Adesão Intercelular/metabolismo , Antígeno-1 Associado à Função Linfocitária/metabolismo , Monócitos/metabolismo , Quimiocina CCL21/genética , Quimiocina CCL21/farmacologia , Células Dendríticas/citologia , Células Dendríticas/efeitos dos fármacos , Regulação da Expressão Gênica , Humanos , Molécula 1 de Adesão Intercelular/genética , Molécula 1 de Adesão Intercelular/farmacologia , Ligantes , Antígeno-1 Associado à Função Linfocitária/genética , Monócitos/citologia , Monócitos/efeitos dos fármacos , Cultura Primária de Células , Agregados Proteicos , Ligação Proteica , Transporte Proteico , Transdução de Sinais , Solubilidade
13.
Clin Dev Immunol ; 2013: 789814, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24319468

RESUMO

The gut mucosa undergoes continuous antigenic exposure from food antigens, commensal flora derived ligands, and pathogens. This constant stimulation results in controlled inflammatory responses that are effectively suppressed by multiple factors. This tight regulation, necessary to maintain intestinal homeostasis, is affected during inflammatory bowel diseases (IBD) resulting in altered immune responses to harmless microorganisms. Dendritic cells (DCs) are sentinels of immunity, located in peripheral and lymphoid tissues, which are essential for homeostasis of T cell-dependent immune responses. The expression of a particular set of pathogen recognition receptors allows DCs to initiate immune responses. However, in the absence of danger signals, different DC subsets can induce active tolerance by inducing regulatory T cells (Treg), inhibiting inflammatory T helper cell responses, or both. Interestingly, several protocols to generate clinical grade tolerogenic DC (tol-DCs) in vitro have been described, opening the possibility to restore the intestinal homeostasis to bacterial flora by cellular therapy. In this review, we discuss different DC subsets and their role in IBD. Additionally, we will review preclinical studies performed in animal models while describing recent characterization of tol-DCs from Crohn's disease patients for clinical application.


Assuntos
Células Dendríticas/imunologia , Tolerância Imunológica , Doenças Inflamatórias Intestinais/imunologia , Animais , Antígenos/imunologia , Doença de Crohn/imunologia , Doença de Crohn/terapia , Células Dendríticas/metabolismo , Modelos Animais de Doenças , Humanos , Imunoterapia , Doenças Inflamatórias Intestinais/terapia , Fenótipo
14.
PLoS One ; 7(12): e52456, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-23300676

RESUMO

Dendritic cells have been investigated in clinical trials, predominantly with the aim of stimulating immune responses against tumours or infectious diseases. Thus far, however, no clinical studies have taken advantage of their specific immunosuppressive potential. Tolerogenic DCs may represent a new therapeutic strategy for human immune-based diseases, such as Crohn's disease, where the perturbations of the finely tuned balance between the immune system and the microflora result in disease. In the present report, we describe the generation of tolerogenic DCs from healthy donors and Crohn's disease patients using clinical-grade reagents in combination with dexamethasone as immunosuppressive agent and characterize their response to maturation stimuli. Interestingly, we found out that dexamethasone-conditioned DCs keep their tolerogenic properties to Gram-negative bacteria. Other findings included in this study demonstrate that the combination of dexamethasone with a specific cytokine cocktail yielded clinical-grade DCs with the following characteristics: a semi-mature phenotype, a pronounced shift towards anti-inflammatory versus inflammatory cytokine production and low T-cell stimulatory properties. Importantly, in regard to their clinical application, the tolerogenic phenotype of DCs remained stable after the elimination of dexamethasone and after a second stimulation with LPS or bacteria. All these properties make this cell product suitable to be tested in clinical trials of inflammatory conditions including Crohn's disease.


Assuntos
Células Dendríticas/efeitos dos fármacos , Células Dendríticas/microbiologia , Dexametasona/farmacologia , Enterobacteriaceae/fisiologia , Tolerância Imunológica/efeitos dos fármacos , Antígenos de Bactérias/imunologia , Estudos de Casos e Controles , Doença de Crohn/imunologia , Citocinas/biossíntese , Células Dendríticas/imunologia , Células Dendríticas/metabolismo , Enterobacteriaceae/imunologia , Humanos , Monócitos/citologia , Fenótipo , Linfócitos T/imunologia , Linfócitos T/microbiologia
15.
Immunol Lett ; 134(2): 167-73, 2011 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-20933012

RESUMO

Dendritic cells are a heterogeneous population of bone marrow derived leucocytes that play a crucial role in both pathogen recognition and the initiation of primary T cell immune responses. Plasmacytoid dendritic cells (pDCs), also known as natural interferon-producing cells, comprise one of two major human dendritic cell subsets that strongly influences immune balance. pDCs remain a poorly characterized subset. Several studies have suggested the existence of a close phenotypic and functional relationship between B-cells and pDCs. The surface reactivity of a panel of 96 monoclonal antibodies submitted to the ninth Human Leukocyte Differentiation Antigens workshop (HLDA9) B cell section was analyzed using pDCs as target cells. The results showed that eight of the mAbs reacted positively on pDCs: CD86, CD229, CD319, CD305, CD184, CD84, CD85g and FcɛRIa, confirming previously published reports. Interestingly, this study also revealed the expression of eight surface molecules not previously described on pDCs, including CD352(NTBA), CD272(BTLA), CD357(GITR), CD48, CD270(HVEM), Galectin-3, CD148, and CD361. The present report summarizes the expression of these molecules on freshly isolated pDCs. Significantly, we have identified several new molecules expressed by these intriguing cells, ones we believe will open new avenues for the study of pDC functionality and their role in human health and diseases.


Assuntos
Anticorpos Monoclonais/imunologia , Antígenos CD/imunologia , Células Dendríticas/imunologia , Humanos , Imunofenotipagem
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA