Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 30
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
2.
mSphere ; 4(5)2019 09 04.
Artigo em Inglês | MEDLINE | ID: mdl-31484738

RESUMO

The demand for a prophylactic vaccine against methicillin-resistant Staphylococcus aureus (MRSA) has motivated numerous dedicated research groups to design and develop such a vaccine. In this study, we have developed a multivalent vaccine, Sta-V5, composed of five conserved antigens involved in three important virulence mechanisms. This prototype vaccine conferred up to 100% protection against multiple epidemiologically relevant S. aureus isolates in five different murine disease models. The vaccine not only elicits functional antibodies that mediate opsonophagocytic killing of S. aureus but also mounts robust antigen-specific T-cell responses. In addition, our data implied that γδ T cells contribute to the protection induced by Sta-V5 in a murine skin infection model.IMPORTANCE Staphylococcus aureus infections, especially MRSA infections, are becoming a major global health issue and are resulting in mortality rates that are increasing every year. However, an effective vaccine is lacking due to the complexity of the infection process of S. aureus In this study, we found that the addition of two novel protein components to three well-studied vaccine candidates significantly improved the efficacy of the combined vaccine. Furthermore, the five-component vaccine not only elicits a robust antibody response but also induces cytokine secretion by T cells, making it a promising vaccine candidate to fill the void.

3.
Mol Ther ; 26(2): 354-365, 2018 02 07.
Artigo em Inglês | MEDLINE | ID: mdl-29310916

RESUMO

Gamma delta T (γδT) lymphocytes are primed for rapid function, including cytotoxicity toward cancer cells, and are a component of the immediate stress response. Following activation, they can function as professional antigen-presenting cells. Chimeric antigen receptors (CARs) work by focusing T cell function on defined cell surface tumor antigens and provide essential costimulation for robust activation. Given the natural tropism of γδT cells for the tumor microenvironment, we hypothesized that their transduction with CARs might enhance cytotoxicity while retaining their ability to migrate to tumor and act as antigen-presenting cells to prolong the intratumoral immune response. Using a GD2-targeting CAR as a model system, we showed that γδT cells of both Vδ1 and Vδ2 subsets could be expanded and transduced to sufficient numbers for clinical studies. The CAR added to the cells' innate cytotoxicity by enhancing GD2-specific killing of GD2-expressing cancer cell lines. Migration toward tumor cells in vitro was not impaired by the presence of the CAR. Expanded CAR-transduced Vδ2 cells retained the ability to take up tumor antigens and cross presented the processed peptide to responder alpha beta T (αßT) lymphocytes. γδ CAR-T cell products show promise for evaluation in clinical studies of solid tumors.


Assuntos
Receptores de Antígenos de Linfócitos T gama-delta/metabolismo , Receptores de Antígenos Quiméricos/metabolismo , Subpopulações de Linfócitos T/imunologia , Subpopulações de Linfócitos T/metabolismo , Apresentação do Antígeno/imunologia , Células Apresentadoras de Antígenos/imunologia , Células Apresentadoras de Antígenos/metabolismo , Antígenos de Neoplasias/imunologia , Biomarcadores , Linhagem Celular Tumoral , Apresentação Cruzada/imunologia , Citotoxicidade Imunológica/imunologia , Humanos , Imunoterapia Adotiva , Ativação Linfocitária/imunologia , Fenótipo , Receptores de Antígenos de Linfócitos T gama-delta/genética , Receptores de Antígenos Quiméricos/genética
4.
J Heart Lung Transplant ; 37(4): 451-457, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-28554587

RESUMO

BACKGROUND: Since 1996, ABO-incompatible heart transplantation has been undertaken by performing whole-body plasma exchange to remove isohemagglutinins using the cardiopulmonary bypass (CPB) circuit at the time of transplantation. This requires large volumes of donated blood and blood products, causes hemodynamic instability during the exchange transfusion, and limits practical use to small children. We sought to determine the efficacy of anti-A/B immunoadsorption within the CPB circuit on removal of isohemagglutinins in an ex vivo setting before its use clinically. METHODS: An anti-A/B immunoadsorption column was placed into a CPB circuit mimicking a typical ABO-incompatible transplant patient, which had been primed with type O whole human blood. Samples were taken for determination of isohemagglutinin titers following each plasma volume pass through the anti-A/B immunoadsorption column. RESULTS: There was a linear decrease of at least 1 dilution seen in both anti-A and anti-B IgG and IgM antibodies with each plasma volume pass through the column. This predictable removal allowed the formulation of selection criteria for ABO-incompatible heart transplantation given the reciprocal of titer and patient weight. This degree of predictability allowed us to use it successfully in the clinical setting, reducing antibodies to an undetectable level during ABO-incompatible heart transplantation. CONCLUSIONS: The incorporation of an anti-A/B immunoadsorption column into the extracorporeal circuit reduces allogeneic blood product requirement for ABO-incompatible heart transplantation, while providing efficacious removal of anti-A and anti-B isohemagglutinins. This can be undertaken within the time period of CPB before graft reperfusion and expands the potential recipient pool to larger patients with higher isohemagglutinin titers.


Assuntos
Sistema do Grupo Sanguíneo ABO , Incompatibilidade de Grupos Sanguíneos , Ponte Cardiopulmonar/métodos , Transplante de Coração/métodos , Técnicas de Imunoadsorção , Estudos de Viabilidade , Hemaglutininas , Humanos , Modelos Cardiovasculares , Modelagem Computacional Específica para o Paciente
5.
Mol Ther ; 25(5): 1234-1247, 2017 05 03.
Artigo em Inglês | MEDLINE | ID: mdl-28341563

RESUMO

Chimeric antigen receptors (CARs) combine T cell activation with antibody-mediated tumor antigen specificity, bypassing the need for T cell receptor (TCR) ligation. A limitation of CAR technology is on-target off-tumor toxicity caused by target antigen expression on normal cells. Using GD2 as a model cancer antigen, we hypothesized that this could be minimized by using T cells expressing Vγ9Vδ2 TCR, which recognizes transformed cells in a major histocompatibility complex (MHC)-unrestricted manner, in combination with a co-stimulatory CAR that would function independently of the TCR. An anti-GD2 CAR containing a solitary endodomain derived from the NKG2D adaptor DAP10 was expressed in Vγ9Vδ2+ T cells. Differential ligation of the CAR and/or TCR using antibody-coated beads showed that pro-inflammatory cytokine response depended on activation of both receptors. Moreover, in killing assays, GD2-expressing neuroblastoma cells that engaged the Vγ9Vδ2 TCR were efficiently lysed, whereas cells that expressed GD2 equivalently but did not engage the Vγ9Vδ2 TCR were untouched. Differentiation between X-on tumor and X-off tumor offers potential for safer immunotherapy and broader target selection.


Assuntos
Antígenos de Neoplasias/genética , Gangliosídeos/química , Proteínas Mutantes Quiméricas/genética , Receptores de Antígenos de Linfócitos T/genética , Linfócitos T/imunologia , Antígenos de Neoplasias/imunologia , Antígenos CD28/genética , Antígenos CD28/imunologia , Complexo CD3/genética , Complexo CD3/imunologia , Linhagem Celular Tumoral , Técnicas de Cocultura , Citotoxicidade Imunológica , Gangliosídeos/imunologia , Expressão Gênica , Humanos , Imunoterapia/métodos , Ativação Linfocitária , Proteínas Mutantes Quiméricas/imunologia , Neurônios/imunologia , Neurônios/patologia , Engenharia de Proteínas/métodos , Receptores de Antígenos de Linfócitos T/imunologia , Linfócitos T/citologia
6.
Arthritis Res Ther ; 18(1): 140, 2016 06 14.
Artigo em Inglês | MEDLINE | ID: mdl-27301320

RESUMO

BACKGROUND: The mechanisms underlying tolerance induction and maintenance in autoimmune arthritis remain elusive. In a mouse model of rheumatoid arthritis, collagen type II (CII)-induced arthritis, we explore the contribution of B cells to antigen-specific tolerance. METHODS: To generate expression of the CII-peptide specifically on B-cell major histocompatibility complex type II, lentiviral-based gene therapy including a B-cell-specific Igk promoter was used. RESULTS: Presentation of the CII-peptide on B cells significantly reduced the frequency and severity of arthritis as well as the serum levels of CII -specific IgG antibodies. Further, both frequency and suppressive function of regulatory T cells were increased in tolerized mice. Adoptive transfer of regulatory T cells from tolerized mice to naïve mice ameliorated the development of CII-induced arthritis. CONCLUSION: Our data suggest that endogenous presentation of the CII-peptide on B cells is one of the key contributors to arthritis tolerance induction and maintenance.


Assuntos
Artrite Experimental/imunologia , Artrite Reumatoide/imunologia , Linfócitos B/imunologia , Colágeno Tipo II/imunologia , Tolerância Imunológica/imunologia , Transferência Adotiva , Animais , Apresentação do Antígeno/imunologia , Ensaio de Imunoadsorção Enzimática , Epitopos de Linfócito T/imunologia , Citometria de Fluxo , Imunofluorescência , Epitopos Imunodominantes/imunologia , Ativação Linfocitária/imunologia , Masculino , Camundongos , Camundongos Endogâmicos DBA
7.
PLoS One ; 11(5): e0154630, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27159398

RESUMO

Here, we investigate induction of immunological tolerance by lentiviral based gene therapy in a mouse model of rheumatoid arthritis, collagen II-induced arthritis (CIA). Targeting the expression of the collagen type II (CII) to antigen presenting cells (APCs) induced antigen-specific tolerance, where only 5% of the mice developed arthritis as compared with 95% of the control mice. In the CII-tolerized mice, the proportion of Tregs as well as mRNA expression of SOCS1 (suppressors of cytokine signaling 1) increased at day 3 after CII immunization. Transfer of B cells or non-B cell APC, as well as T cells, from tolerized to naïve mice all mediated a certain degree of tolerance. Thus, sustainable tolerance is established very early during the course of arthritis and is mediated by both B and non-B cells as APCs. This novel approach for inducing tolerance to disease specific antigens can be used for studying tolerance mechanisms, not only in CIA but also in other autoimmune diseases.


Assuntos
Antígenos/imunologia , Artrite Experimental/terapia , Colágeno Tipo II/administração & dosagem , Terapia Genética , Tolerância Imunológica , Animais , Anticorpos/imunologia , Artrite Experimental/sangue , Artrite Experimental/imunologia , Linfócitos B/imunologia , Colágeno Tipo II/imunologia , Citocinas/sangue , Citometria de Fluxo , Masculino , Camundongos , Camundongos Endogâmicos DBA , Linfócitos T/imunologia
8.
Oncoimmunology ; 5(1): e1025194, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26942051

RESUMO

Gamma delta T lymphocytes (γδT cells) have pleiotropic properties including innate cytotoxicity, which make them attractive effectors for cancer immunotherapy. Combination treatment with zoledronic acid and IL-2 can activate and expand the most common subset of blood γδT, which express the Vγ9Vδ2 T cell receptor (TCR) (Vδ2 T cells). Vγ9Vδ2 T cells are equipped for antibody-dependent cell-mediated cytotoxicity (ADCC) through expression of the low-affinity FcγR CD16. GD2 is a highly ranked tumor associated antigen for immunotherapy due to bright expression on the cell surface, absent expression on normal tissues and availability of therapeutic antibodies with known efficacy in neuroblastoma. To explore the hypothesis that zoledronic acid, IL-2 and anti-GD2 antibodies will synergize in a therapeutic combination, we evaluated in vitro cytotoxicity and tumor growth inhibition in the GD2 expressing cancers neuroblastoma and Ewing's sarcoma. Vδ2 T cells exert ADCC against GD2-expressing Ewing's sarcoma and neuroblastoma cell lines, an effect which correlates with the brightness of GD2 expression. In an immunodeficient mouse model of small established GD2-expressing Ewing's sarcoma or neuroblastoma tumors, the combination of adoptively transferred Vδ2+ T cells, expanded in vitro with zoledronic acid and IL-2, with anti-GD2 antibody ch14.18/CHO, and with systemic zoledronic acid, significantly suppressed tumor growth compared to antibody or γδT cell-free controls. Combination treatment using ch14.18/CHO, zoledronic acid and IL-2 is more effective than their use in isolation. The already-established safety profiles of these agents make testing of the combination in GD2 positive cancers such as neuroblastoma or Ewing's sarcoma both rational and feasible.

9.
Oncoimmunology ; 4(3): e973808, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25949890

RESUMO

Gamma delta T cells (γδT) are potent mediators of antitumor cytotoxicity and have shown promising efficacy in early phase clinical trials. Most is known about the tumoricidal properties of cells bearing the Vδ2 T cell receptor chain, but recent studies have demonstrated that cells with the Vδ1 chain and those with neither Vδ1 nor Vδ2 chains have properties which may make them more attractive anticancer effectors in adoptive immunotherapy.

10.
Biomaterials ; 35(29): 8406-15, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-24985735

RESUMO

Formulations of cationic liposomes and polymers readily self-assemble by electrostatic interactions with siRNA to form cationic nanoparticles which achieve efficient transfection and silencing in vitro. However, the utility of cationic formulations in vivo is limited due to rapid clearance from the circulation, due to their association with serum proteins, as well as systemic and cellular toxicity. These problems may be overcome with anionic formulations but they provide challenges of self-assembly and transfection efficiency. We have developed anionic, siRNA nanocomplexes utilizing anionic PEGylated liposomes and cationic targeting peptides that overcome these problems. Biophysical measurements indicated that at optimal ratios of components, anionic PEGylated nanocomplexes formed spherical particles and that, unlike cationic nanocomplexes, were resistant to aggregation in the presence of serum, and achieved significant gene silencing although their non-PEGylated anionic counterparts were less efficient. We have evaluated the utility of anionic nanoparticles for the treatment of neuronal diseases by administration to rat brains of siRNA to BACE1, a key enzyme involved in the formation of amyloid plaques. Silencing of BACE1 was achieved in vivo following a single injection of anionic nanoparticles by convection enhanced delivery and specificity of RNA interference verified by 5' RACE-PCR and Western blot analysis of protein.


Assuntos
Secretases da Proteína Precursora do Amiloide/genética , Ácido Aspártico Endopeptidases/genética , Lipossomos/química , Nanopartículas/química , Interferência de RNA , RNA Interferente Pequeno/administração & dosagem , Animais , Ânions/química , Encéfalo/metabolismo , Encefalopatias/genética , Encefalopatias/terapia , Linhagem Celular , Terapia Genética , Humanos , Lipídeos/química , Masculino , Polietilenoglicóis/química , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/uso terapêutico , Ratos , Ratos Wistar , Transfecção/métodos
11.
Clin Cancer Res ; 20(22): 5720-32, 2014 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-24893631

RESUMO

PURPOSE: The majority of circulating human γδT lymphocytes are of the Vγ9Vδ2 lineage, and have T-cell receptor (TCR) specificity for nonpeptide phosphoantigens. Previous attempts to stimulate and expand these cells have therefore focused on stimulation using ligands of the Vγ9Vδ2 receptor, whereas relatively little is known about variant blood γδT subsets and their potential role in cancer immunotherapy. EXPERIMENTAL DESIGN: To expand the full repertoire of γδT without bias toward specific TCRs, we made use of artificial antigen-presenting cells loaded with an anti γδTCR antibody that promoted unbiased expansion of the γδT repertoire. Expanded cells from adult blood donors were sorted into 3 populations expressing respectively Vδ2 TCR chains (Vδ2(+)), Vδ1 chains (Vδ1(+)), and TCR of other δ chain subtypes (Vδ1(neg)Vδ2(neg)). RESULTS: Both freshly isolated and expanded cells showed heterogeneity of differentiation markers, with a less differentiated phenotype in the Vδ1 and Vδ1(neg)Vδ2(neg) populations. Expanded cells were largely of an effector memory phenotype, although there were higher numbers of less differentiated cells in the Vδ1(+) and Vδ1(neg)Vδ2(neg) populations. Using neuroblastoma tumor cells and the anti-GD2 therapeutic mAb ch14.18 as a model system, all three populations showed clinically relevant cytotoxicity. Although killing by expanded Vδ2 cells was predominantly antibody dependent and proportionate to upregulated CD16, Vδ1 cells killed by antibody-independent mechanisms. CONCLUSIONS: In conclusion, we have demonstrated that polyclonal-expanded populations of γδT cells are capable of both antibody-dependent and -independent effector functions in neuroblastoma.


Assuntos
Citotoxicidade Imunológica , Neuroblastoma/imunologia , Neuroblastoma/metabolismo , Receptores de Antígenos de Linfócitos T gama-delta/metabolismo , Subpopulações de Linfócitos T/imunologia , Subpopulações de Linfócitos T/metabolismo , Células Apresentadoras de Antígenos/imunologia , Células Apresentadoras de Antígenos/metabolismo , Técnicas de Cultura de Células , Diferenciação Celular , Linhagem Celular Tumoral , Variação Genética , Humanos , Região de Junção de Imunoglobulinas/genética , Memória Imunológica , Imunofenotipagem , Leucócitos Mononucleares/imunologia , Leucócitos Mononucleares/metabolismo , Neuroblastoma/genética , Fenótipo , Receptores de IgG/genética , Receptores de IgG/metabolismo , Subpopulações de Linfócitos T/citologia
12.
Oncoimmunology ; 3(1): e27572, 2014 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-24734216

RESUMO

γδ T cells contribute to the front line of lymphoid antitumor surveillance and bridge the gap between innate and adaptive immunity. They can be readily expanded to high numbers in vivo and in vitro, starting from the blood of cancer patients, and a number of Phase I trials have demonstrated that these cells can be employed in cancer immunotherapy. Sufficient patients have received γδ T cell-based immunotherapies in the context of clinical trials to evaluate their utility, and to inform the direction of new trials. A systematic approach was used to identify Phase I, Phase II, and feasibility studies testing γδ T cell-based immunotherapy in cancer patients. Studies were excluded from further analysis if they did not provide patient-specific data. Data were compiled to evaluate efficacy, with stratification by treatment approach. When possible, comparisons were made with the efficacy of second-line conventional therapeutic approaches for the same malignancy. Twelve eligible studies were identified, providing information on 157 patients who had received γδ T cell-based immunotherapy. The comparison of objective response data suggests that γδ T cell-based immunotherapy is superior to current second-line therapies for advanced renal cell carcinoma and prostate cancer, but not for non-small cell lung carcinoma. An evaluation of pooled data from 132 published in vitro experiments shows a consistent improvement in the cytotoxicity of γδ T cells in the presence of antitumor antibodies. Immunotherapy using γδ T cells alone shows promising clinical activity, but there is a strong preclinical rationale for combining this treatment modality with cancer-targeting antibodies to augment its efficacy.

13.
Drug Discov Today ; 19(6): 787-793, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24681060

RESUMO

Manipulation of the human immune system is becoming more of a therapeutic focus as a treatment option or complement. Prominent examples are the increasing use of monoclonal antibodies in combating malignant tumours, and the numerous adoptive immunotherapy trials underway. One important aspect of any use of the human immune system in this regard is to harness the power of professional antigen-presenting cells (pAPC), that is, dendritic cells (DC), to direct immune responses. Here, we review how recent findings regarding the biology of γδT cells have revealed that they, surprisingly, could serve as convenient tools for this purpose, in that they combine innate cytotoxic cell and pAPC functions in one cell type, with potential benefits in cancer immunotherapy and infectious disease.


Assuntos
Imunidade Celular/imunologia , Regeneração/imunologia , Linfócitos T/imunologia , Linfócitos T/microbiologia , Animais , Linhagem Celular Transformada , Doenças Transmissíveis/imunologia , Humanos , Neoplasias/imunologia , Neoplasias/terapia , Linfócitos T/patologia
14.
Small ; 10(1): 78-82, 2014 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-23894081

RESUMO

Cell electrospinning and aerodynamically assisted bio-threading are novel bioplatforms for directly forming large quantities of cell-laden scaffolds for creating living sheets and vessels in three-dimensions. The functional biological architectures generated will be useful in both the laboratory and the clinic.


Assuntos
Engenharia Tecidual/métodos , Tecidos Suporte/química , Animais , Materiais Biocompatíveis , Eletroquímica , Camundongos
15.
Clin Dev Immunol ; 2013: 345092, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24371448

RESUMO

Reestablishment of tolerance induction in rheumatoid arthritis (RA) would be an optimal treatment with few, if any, side effects. However, to develop such a treatment further insights in the immunological mechanisms governing tolerance are needed. We have developed a model of antigen-specific tolerance in collagen type II (CII) induced arthritis (CIA) using lentivirus-based gene therapy. The immunodominant epitope of CII was inserted into a lentivirus vector to achieve expression on the MHC class II molecule and the lentiviral particles were subsequently intravenously injected at different time points during CIA. Injection of lentiviral particles in early phases of CIA, that is, at day 7 or day 26 after CII immunisation, partially prevented development of arthritis, decreased the serum levels of CII-specific IgG antibodies, and enhanced the suppressive function of CII-specific T regulatory cells. When lentiviral particles were injected during manifest arthritis, that is, at day 31 after CII immunisation, the severity of arthritis progression was ameliorated, the levels of CII-specific IgG antibodies decreased and the proportion of T regulatory cells increased. Thus, antigen-specific gene therapy is effective when administered throughout the inflammatory course of arthritis and offers a good model for investigation of the basic mechanisms during tolerance in CIA.


Assuntos
Artrite Experimental/genética , Artrite Experimental/imunologia , Colágeno Tipo II/genética , Colágeno Tipo II/imunologia , Epitopos/genética , Animais , Anticorpos/sangue , Anticorpos/imunologia , Especificidade de Anticorpos/imunologia , Artrite Experimental/terapia , Autoanticorpos/sangue , Autoanticorpos/imunologia , Ordem dos Genes , Terapia Genética , Vetores Genéticos/administração & dosagem , Vetores Genéticos/genética , Tolerância Imunológica , Imunização , Imunoglobulina G/sangue , Imunoglobulina G/imunologia , Lentivirus/genética , Masculino , Subpopulações de Linfócitos T/imunologia , Linfócitos T Reguladores/imunologia , Fatores de Tempo
16.
Biomacromolecules ; 14(3): 761-70, 2013 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-23339543

RESUMO

Efficient delivery of small interfering RNA (siRNA) remains the greatest technological barrier to the clinical implementation of RNA interference strategies. We are investigating the relationship between the biophysical properties of siRNA nanocomplexes and their transfection efficiency as an approach to the generation of improved formulations. Peptide-based formulations are of great interest, and so in this study we have compared nanocomplex formulations for siRNA delivery containing linear and branched oligolysine or oligoarginine peptides. Peptides were combined with cationic liposomes in siRNA formulations and compared for transfection efficiency, siRNA packaging efficiency, biophysical properties, and particle stability. Nanocomplexes containing linear peptides were more condensed and stable than branched peptide formulations; however, their silencing activity was lower, suggesting that their greater stability might limit siRNA release within the cell. Thus, differences in transfection appeared to be associated with differences in packaging and stability, indicating the importance of optimizing this feature in siRNA nanocomplexes.


Assuntos
Nanoestruturas/química , Peptídeos/química , Interferência de RNA , RNA Interferente Pequeno/genética , Animais , Cátions , Linhagem Celular Tumoral , Proliferação de Células , Sistemas de Liberação de Medicamentos , Lipossomos , Luciferases/análise , Luciferases/metabolismo , Camundongos , Microscopia Confocal , Microscopia Eletrônica de Transmissão , Tamanho da Partícula , Transfecção
17.
Oncoimmunology ; 1(9): 1652-1654, 2012 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-23264926

RESUMO

Following activation, γδ T cells display many properties of lymphocytes from the innate immune system, yet how they mediate antigen presentation remains an open conundrum. In humans, circulating γδ T cells that express the Vγ9Vδ2 T-cell receptor become reversibly licensed for professional antigen presentation only upon interaction with a target cell opsonized with IgGs.

18.
Small ; 8(16): 2495-500, 2012 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-22648794

RESUMO

Bio-sprays can directly form pre-organized cell-bearing structures for applications ranging from engineering functional tissues to the forming of cultures, most useful for modeling disease, to the discovery and development of drugs. Bio-electrosprays and aerodynamically assisted bio-jets, are leading approaches that have been demonstrated as having far-reaching ramifications for regenerative biology and medicine.


Assuntos
Células/metabolismo , Engenharia Tecidual/métodos , Animais , Divisão Celular , Linhagem Celular Tumoral , Forma Celular , Sobrevivência Celular , Citometria de Fluxo , Medições Luminescentes , Camundongos
19.
J Immunotoxicol ; 9(3): 259-66, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22632132

RESUMO

Dendritic cells are characterized by the ability to induce primary antigen-specific immune responses in both major histocompatibility complex (MHC) Class I-restricted CD8 cells and MHC Class II-restricted CD4 cells. This professional antigen presentation function is associated with the up-regulation of co-stimulatory molecules and Class II MHC. While it has been recognized that several types of innate lymphocytes in mouse and humans can express co-stimulatory molecules and present antigen, the property of antigen presentation to elicit responses in naïve cells has been considered the exclusive domain of the dendritic cell. This concept has been challenged through the description of innate lymphocytes, capable of killing using NK receptors, but also up-regulating co-stimulatory molecules and driving the antigen-specific proliferation of naïve lymphocytes to the same extent as dendritic cells. Interferon (IFN)-γ secreting killer dendritic cells (IKDC) have been described in mice and share immunophenotypic properties of both dendritic cells and natural killer cells. Human blood γδ T-lymphocytes have innate tumor cell killing properties by both antibody-dependent and natural killer receptor-dependent mechanisms. This article reviews data from the authors' own laboratory showing a particular feature in common between the mouse IKDC and human blood γδ T-lymphocytes; namely their requirement for interaction with a target cell for specific licensing for professional antigen presentation.


Assuntos
Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , Células Dendríticas/imunologia , Células Matadoras Naturais/imunologia , Receptores de Antígenos de Linfócitos T gama-delta/imunologia , Animais , Antígenos de Histocompatibilidade Classe I/imunologia , Antígenos de Histocompatibilidade Classe II/imunologia , Humanos , Imunidade Celular/fisiologia , Imunidade Inata/fisiologia , Interferon gama/imunologia , Camundongos
20.
J Immunol ; 188(4): 1708-16, 2012 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-22250090

RESUMO

Activated human blood γδ T cells have also been previously demonstrated to behave as professional APCs, although the processes that control APC function have not been characterized. n this study, we show that the acquisition of potent APC function by human blood γδ T cells is achieved after physical interaction with an Ab-coated target cell, a process that we refer to as licensing. In cancer models, licensing of γδ T cells by tumor-reactive mAbs promotes the uptake of tumor Ags and professional presentation to tumor-reactive αß T cells. We propose that licensing by Ab is a mechanism whereby the adaptive properties of γδ T cells are induced by their innate functions in a spatially and temporally controlled manner.


Assuntos
Apresentação do Antígeno , Antígenos de Neoplasias/imunologia , Neoplasias/imunologia , Fagocitose , Subpopulações de Linfócitos T/imunologia , Anticorpos Monoclonais/imunologia , Anticorpos Antineoplásicos/imunologia , Células Apresentadoras de Antígenos/imunologia , Linhagem Celular , Humanos , Ativação Linfocitária , Receptores de Antígenos de Linfócitos T alfa-beta/imunologia , Receptores de Antígenos de Linfócitos T gama-delta/imunologia
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA