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1.
Fish Shellfish Immunol ; 88: 415-423, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30872029

RESUMO

The hematopoietic organ (HO) of the giant freshwater prawn Macrobrachium rosenbergii is a discrete, whitish mass located in the epigastric region of the cephalothorax, posterior to the brain. It is composed of hematopoietic cells arranged in a thick layer of numerous lobules that surround a central hemal sinus from which they are separated by a thin sheath. At the center of the sinus is the muscular cor frontale. The lobules extend radially outward from the sinus in three developmental zones. Basal Zone 1 nearest the sinus contains large hematopoietic stem cells with euchromatic nuclei that stain positive for proliferation cell nuclear antigen (PCNA). Zone 2 contains smaller, actively dividing cells as indicated by positive 5-bromo-20-deoxyuridine (BrdU) staining. Distal Zone 3 contains small, loosely packed cells with heterochromatic nuclei, many cytoplasmic granules and vesicles indicating that they will eventually differentiate into hemocytes and enter circulation. Three main arteries, namely the ophthalmic and the 2 branches of the antennary, connect the heart to the HO. Use of India ink and 0.1 µm fluorescent micro-beads injected into the heart revealed that the cor frontale could immediately remove foreign particles from hemolymph by filtration. Fluorescent beads were also detected in the hematopoietic tissue at 30 min after injection, indicating that it could be penetrated by foreign particles. However, the fluorescent signal completely disappeared from the whole HO after 4 h, indicating its role in removal of foreign particles. In conclusion, the present study demonstrated for the first time the detailed histological structures of the HO of M. rosenbergii and its relationship to hematopoiesis and removal of foreign particles from hemolymph.


Assuntos
Sistema Hematopoético/citologia , Sistema Hematopoético/imunologia , Palaemonidae/imunologia , Animais , Proteínas de Artrópodes/química , Células-Tronco Hematopoéticas , Hemócitos/imunologia , Hemolinfa , Palaemonidae/anatomia & histologia , Fagocitose , Antígeno Nuclear de Célula em Proliferação/química
2.
Cancer ; 125(6): 963-971, 2019 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-30521100

RESUMO

BACKGROUND: Langerhans cell histiocytosis (LCH) is a rare myeloid neoplasm characterized by the presence of abnormal CD1a-positive (CD1a+ )/CD207+ histiocytes. Hemophagocytic lymphohistiocytosis (HLH) represents a spectrum of hyperinflammatory syndromes typified by the dysregulated activation of the innate and adaptive immune systems. Patients with LCH, particularly those with multisystem (MS) involvement, can develop severe hyperinflammation mimicking that observed in HLH. Nevertheless, to the authors' knowledge, little is known regarding the prevalence, timing, risk factors for development, and outcomes of children and young adults who develop HLH within the context of MS-LCH (hereafter referred to LCH-associated HLH). METHODS: To gain further insights, the authors conducted a retrospective, multicenter study and collected data regarding all patients diagnosed with MS-LCH between 2000 and 2015. RESULTS: Of 384 patients with MS-LCH, 32 were reported by their primary providers to have met the diagnostic criteria for HLH, yielding an estimated 2-year cumulative incidence of 9.3% ± 1.6%. The majority of patients developed HLH at or after the diagnosis of MS-LCH, and nearly one-third (31%) had evidence of an intercurrent infection. Patient age <2 years at the time of diagnosis of LCH; female sex; LCH involvement of the liver, spleen, and hematopoietic system; and a lack of bone involvement each were found to be independently associated with an increased risk of LCH-associated HLH. Patients with MS-LCH who met the criteria for HLH had significantly poorer 5-year survival compared with patients with MS-LCH who did not meet the criteria for HLH (69% vs 97%; P < .0001). CONCLUSIONS: Given its inferior prognosis, further efforts are warranted to enhance the recognition and optimize the treatment of patients with LCH-associated HLH.


Assuntos
Sistema Hematopoético/imunologia , Histiocitose de Células de Langerhans/complicações , Fígado/imunologia , Linfo-Histiocitose Hemofagocítica/epidemiologia , Baço/imunologia , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Sistema Hematopoético/patologia , Histiocitose de Células de Langerhans/imunologia , Humanos , Lactente , Recém-Nascido , Fígado/patologia , Linfo-Histiocitose Hemofagocítica/imunologia , Masculino , Prognóstico , Estudos Retrospectivos , Baço/patologia , Adulto Jovem
3.
Dev Comp Immunol ; 88: 70-76, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30003890

RESUMO

Transfection is a powerful tool useful for studying gene function. Establishing transfection methods that enable highly efficient DNA uptake has become increasingly important. The crayfish hematopoietic tissue (Hpt) cell cultures have been proven to be suitable for studies on immunity and cell differentiation in crustaceans including shrimps, but no efficient gene transfer and expression method is available for these cells. Here we report a novel and highly efficient DNA transfection system based on electroporation. This method depends on a recombinant plasmid with the promoter from white spot syndrome virus immediate-early gene wsv249. This plasmid could be introduced into primary cells and efficiently express foreign genes by electroporation. By optimizing different electroporation parameters, more than 30% transfection efficiency could be achieved with the relative viability of cells around 50%. This is the first report of gene introduction to crayfish Hpt cells and will be useful for the expanding our research on crustacean immunity.


Assuntos
Eletroporação/métodos , Sistema Hematopoético/citologia , Plasmídeos/genética , Transfecção/métodos , Animais , Astacoidea/citologia , Astacoidea/genética , Astacoidea/imunologia , Sobrevivência Celular , Células Cultivadas , DNA Viral/genética , Vetores Genéticos/genética , Sistema Hematopoético/imunologia , Regiões Promotoras Genéticas/genética , Células Sf9 , Spodoptera , Vírus da Síndrome da Mancha Branca 1/genética
4.
Leukemia ; 32(2): 492-498, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-28642591

RESUMO

Prior data indicate similar outcomes after transplants from human leukocyte antigen (HLA)-haplotype-matched relatives, HLA-identical siblings and HLA-matched unrelated donors. We used our prospective data set to answer a clinically important question: who is the best donor for a person with acute leukaemia transplanted in first complete remission. Patients were randomly divided into training (n=611) and validation (n=588) sets. A total of 1199 consecutive subjects received a transplant from an HLA-haplotype-matched relative using granulocyte colony-stimulating factor and anti-thymocyte globulin (n=685) or an HLA-identical sibling (n=514); 3-year leukaemia-free survivals (LFSs) were 75 and 74% (P=0.95), respectively. The multivariate model identified three major risk factors for transplant-related mortality (TRM): older donor/recipient age, female-to-male transplants and donor-recipient ABO major-mismatch transplants. A risk score was developed based on these three features. TRMs were 8%, 15% and 31% for subjects with scores of 0-1, 2 and 3, respectively, (P<0.001). Three-year LFSs were 78%, 74% and 58%, respectively, (P=0.003). The risk score was validated in an independent cohort. In conclusion, our data confirm donor source is not significantly correlated with transplant outcomes. Selection of the best donor needs to consider donor-recipient age, matching for gender and ABO incompatibility among persons with acute leukaemia receiving related transplants under our transplant modality.


Assuntos
Sistema do Grupo Sanguíneo ABO/imunologia , Sistema Hematopoético/imunologia , Histocompatibilidade/imunologia , Adolescente , Adulto , Idoso , Soro Antilinfocitário/imunologia , Transplante de Medula Óssea/métodos , Criança , Estudos de Coortes , Seleção do Doador/métodos , Feminino , Sobrevivência de Enxerto/imunologia , Doença Enxerto-Hospedeiro/imunologia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Irmãos , Transplante Homólogo/métodos , Doadores não Relacionados , Adulto Jovem
5.
Comp Med ; 66(4): 308-23, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27538862

RESUMO

Cynomolgus macaques (CYNO; Macaca fascicularis) are a well-established NHP model used for studies in immunology. To provide reference values on the baseline cell distributions in the hematopoietic and lymphoid organs (HLO) of these animals, we used flow cytometry to analyze the peripheral blood, bone marrow, mesenteric lymph nodes, spleen, and thymus of a cohort of male, adult, research-naïve, Mauritian CYNO. Our findings demonstrate that several cell distribution patterns differ between CYNO and humans. First, the CD4(+):CD8(+) T-cell ratio is lower in CYNO compared with humans. Second, the peripheral blood of CYNO contains a population of CD4(+)CD8(+) T cells. Third, the CD31 level was elevated in all organs studied, suggesting that CD31 may not be an accurate marker of recent thymic emigrants within the CD4(+) T cells of CYNO. Finally the B-cell population is lower in CYNO compared with humans. In summary, although the majority of immune cell populations are similar between cynomolgus macaques and humans, several important differences should be considered when using CYNO in immunologic studies. Our current findings provide valuable information to not only researchers but also veterinarians working with CYNO at research centers, in zoos, or in the wild.


Assuntos
Leucócitos/classificação , Macaca fascicularis/anatomia & histologia , Macaca fascicularis/imunologia , Animais , Antígenos CD34/metabolismo , Linfócitos B/citologia , Relação CD4-CD8 , Antígeno CD56/metabolismo , Fatores de Transcrição Forkhead/metabolismo , Sistema Hematopoético/citologia , Sistema Hematopoético/imunologia , Humanos , Subunidade alfa de Receptor de Interleucina-2/metabolismo , Antígenos Comuns de Leucócito/metabolismo , Leucócitos/citologia , Leucócitos/imunologia , Tecido Linfoide/citologia , Tecido Linfoide/imunologia , Macaca fascicularis/sangue , Masculino , Monócitos/citologia , Especificidade de Órgãos , Molécula-1 de Adesão Celular Endotelial a Plaquetas/metabolismo , Especificidade da Espécie , Subpopulações de Linfócitos T/citologia , Subpopulações de Linfócitos T/imunologia
6.
Fish Shellfish Immunol ; 50: 288-96, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26845698

RESUMO

To elucidate proteomic changes of Hpt cells from red claw crayfish, Cherax quadricarinatus, we have carried out isobaric tags for relative and absolute quantitation (iTRAQ) of cellular proteins at both early (1 hpi) and late stage (12 hpi) post white spot syndrome virus (WSSV) infection. Protein database search revealed 594 protein hits by Mascot, in which 17 and 30 proteins were present as differentially expressed proteins at early and late viral infection, respectively. Generally, these differentially expressed proteins include: 1) the metabolic process related proteins in glycolysis and glucogenesis, DNA replication, nucleotide/amino acid/fatty acid metabolism and protein biosynthesis; 2) the signal transduction related proteins like small GTPases, G-protein-alpha stimulatory subunit, proteins bearing PDZ- or 14-3-3-domains that help holding together and organize signaling complexes, casein kinase I and proteins of the MAP-kinase signal transduction pathway; 3) the immune defense related proteins such as α-2 macroglobulin, transglutaminase and trans-activation response RNA-binding protein 1. Taken together, these protein information shed new light on the host cellular response against WSSV infection in a crustacean cell culture.


Assuntos
Proteínas de Artrópodes/genética , Astacoidea/imunologia , Vírus da Síndrome da Mancha Branca 1/fisiologia , Animais , Proteínas de Artrópodes/metabolismo , Astacoidea/genética , Astacoidea/virologia , Sistema Hematopoético/imunologia , Proteômica/métodos , Análise de Sequência de DNA
7.
Haematologica ; 101(1): 5-19, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26721800

RESUMO

Over the last decades, incrementally improved xenograft mouse models, supporting the engraftment and development of a human hemato-lymphoid system, have been developed and now represent an important research tool in the field. The most significant contributions made by means of humanized mice are the identification of normal and leukemic hematopoietic stem cells, the characterization of the human hematopoietic hierarchy, and their use as preclinical therapy models for malignant hematopoietic disorders. Successful xenotransplantation depends on three major factors: tolerance by the mouse host, correct spatial location, and appropriately cross-reactive support and interaction factors such as cytokines and major histocompatibility complex molecules. Each of these can be modified. Experimental approaches include the genetic modification of mice to faithfully express human support factors as non-cross-reactive cytokines, to create free niche space, the co-transplantation of human mesenchymal stem cells, the implantation of humanized ossicles or other stroma, and the implantation of human thymic tissue. Besides the source of hematopoietic cells, the conditioning regimen and the route of transplantation also significantly affect human hematopoietic development in vivo. We review here the achievements, most recent developments, and the remaining challenges in the generation of pre-clinically-predictive systems for human hematology and immunology, closely resembling the human situation in a xenogeneic mouse environment.


Assuntos
Sistema Hematopoético/imunologia , Sistema Linfático/imunologia , Transplante de Células-Tronco Mesenquimais , Timo/transplante , Animais , Xenoenxertos , Humanos , Camundongos , Camundongos SCID , Timo/imunologia
8.
Dev Comp Immunol ; 48(1): 244-53, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25281274

RESUMO

The locust cellular defense is mediated by hemocytes and hematopoietic tissue. In Locusta migratoria, the hemocytes and hematopoietic tissue mutually assist each other in clearing invading pathogens from circulation. A ß-1, 3-glucan infection induces nodule formation and apoptotic, TUNEL positive, cells in the hematopoietic tissue and massive loss of hemocytes in the circulation, calling for instant proliferation of hemocytes and hematopoietic tissue cells to assure continued host cellular defense. As the locust hematopoietic tissue persists at the adult stage, it was originally designated as being the major source for the replenishment process. Revisiting post infection hemocyte proliferation, using immunofluorescence based tests for DNA synthesis and mitosis, evidenced the lack of ß-1, 3-glucan induced cell proliferation in the hematopoietic tissue. Instead these tests identified the circulating hemocytes as the major source for hemocyte replenishment in the circulation. The hematopoietic tissue, however, undergoes a continuous, slow and infection independent regeneration, thereby accumulating potential phagocytes despite infection, and might serve a prophylactic role in containing pathogens in this swarming insect.


Assuntos
Apoptose/imunologia , Hemócitos/citologia , Hemócitos/imunologia , Imunidade Celular/imunologia , Locusta migratoria/imunologia , Animais , Candida albicans/imunologia , Proliferação de Células , Sistema Hematopoético/imunologia , Locusta migratoria/genética , Fagócitos/citologia , Fagócitos/imunologia , Fagocitose/imunologia , Sarcina/imunologia , beta-Glucanas/imunologia
9.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 22(6): 1673-7, 2014 Dec.
Artigo em Chinês | MEDLINE | ID: mdl-25543495

RESUMO

The study was aimed to investigate the effect of anti-mouse CD122 antibody on the hematopoietic repopulating capacity of cord blood CD34⁺ cells in a humanized murine model-non obese diabetic/severe combined immunodeficiency (NOD/SCID) mice. After sublethal irradiation with γ-ray, NOD/SCID mice were intraperitoneally injected with 200 µg mouse isotype control antibody or anti-mouse CD122 antibody. Human cord blood CD34⁺ cells or phosphate-buffered saline (PBS) were injected via the tail vein at 6-8 hours later. Cohort of the mice injected with anti-mice CD122 antibody or control antibody alone were sacrificed at different time point (at week 2, 3, and 4 weeks) after the injection, and the percentage of NK cells in the peripheral blood was analyzed by flow cytometry. To evaluate the effect of anti-mouse CD122 antibody on the repopulating capacity of cord blood CD34⁺ cells in the recipient mice, phenotype analysis was performed in the bone marrow at 6 and 8 weeks after the transplantation. The results showed that the proportion of NK cells in the peripheral blood were (4.6 ± 0.6)% and (5.7 ± 1.7)% at week 2 and 3 after anti-CD122 antibody injection respectively,which decreased by 60%, compared with the mice injected with isotype control antibody. After 6 and 8 weeks of cord blood CD34⁺ cell transplantation,the percentage of human CD45⁺ in the bone marrow of the recipient mice treated with anti-mice CD122 antibody was (63.0 ± 12.2)% and (53.2 ± 16.3)%,respectively,which were dramatically higher than that in the mice treated with isotype control antibody (7.7 ± 3.6)% and (6.1 ± 2.4)%. Moreover,at 8 weeks after transplantation,human CD34⁺ cells appeared significantly in the recipients treated with anti-CD122 antibody. It is concluded that the anti-mouse CD122 antibody enhances the hematopoietic repopulating capacity of cord blood CD34⁺ cells in the NOD/SCID mice through decreasing the proportion of NK cells.


Assuntos
Anticorpos/imunologia , Sangue Fetal/imunologia , Sistema Hematopoético/citologia , Sistema Hematopoético/imunologia , Subunidade beta de Receptor de Interleucina-2/imunologia , Animais , Antígenos CD34 , Medula Óssea , Transplante de Células-Tronco de Sangue do Cordão Umbilical , Transplante de Células-Tronco Hematopoéticas , Humanos , Células Matadoras Naturais , Camundongos , Camundongos Endogâmicos NOD , Camundongos SCID , Transplante Heterólogo
10.
Tissue Antigens ; 82(1): 1-15, 2013 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-23745569

RESUMO

It is well established that interactions between CD4(+) T cells and major histocompatibility complex class II (MHCII) positive antigen-presenting cells (APCs) of hematopoietic origin play key roles in both the maintenance of tolerance and the initiation and development of autoimmune and inflammatory disorders. In sharp contrast, despite nearly three decades of intensive research, the functional relevance of MHCII expression by non-hematopoietic tissue-resident cells has remained obscure. The widespread assumption that MHCII expression by non-hematopoietic APCs has an impact on autoimmune and inflammatory diseases has in most instances neither been confirmed nor excluded by indisputable in vivo data. Here we review and put into perspective conflicting in vitro and in vivo results on the putative impact of MHCII expression by non-hematopoietic APCs--in both target organs and secondary lymphoid tissues--on the initiation and development of representative autoimmune and inflammatory disorders. Emphasis will be placed on the lacunar status of our knowledge in this field. We also discuss new mouse models--developed on the basis of our understanding of the molecular mechanisms that regulate MHCII expression--that constitute valuable tools for filling the severe gaps in our knowledge on the functions of non-hematopoietic APCs in inflammatory conditions.


Assuntos
Doenças Autoimunes/imunologia , Sistema Hematopoético/imunologia , Sistema Hematopoético/patologia , Antígenos de Histocompatibilidade Classe II/metabolismo , Inflamação/imunologia , Animais , Células Apresentadoras de Antígenos/imunologia , Doenças Autoimunes/patologia , Modelos Animais de Doenças , Humanos , Inflamação/patologia , Especificidade de Órgãos/imunologia
11.
Arch Immunol Ther Exp (Warsz) ; 61(1): 15-23, 2013 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-22940878

RESUMO

Homeostasis is a word widely used in the scientific community to refer to the property of a system to maintain its uniformity and functionality. In living organisms, the word refers to the concept enunciated 150 years ago by C. Bernard by which external variations must be compensated for in order to maintain internal conditions compatible with life. This is especially true in the case of highly dynamic system such as the hematopoietic system that requires the coordinated control of cell proliferation and death within specialized microenvironments that are anatomically distinct. As a consequence, hematopoietic cell adhesion and migration must be tightly controlled in order for hematopoietic cells to reach and to be maintained in appropriate microenvironments. The junctional adhesion molecules (JAMs) are adhesion molecules that belong to the immunoglobulin superfamily (IgSf) and that have been initially identified as important players controlling vascular permeability and leukocyte transendothelial migration. This involves the regulated localization of the JAMs at lateral endothelial cell/cell borders and their interaction with leukocyte integrins. More recently, some of the JAM family members have also been found to be expressed by stromal cells and to regulate chemokine secretion within lymphoid organs, acting not only on leukocyte transendothelial migration, but also on hematopoietic cell retention within specialized microenvironments. This review summarizes recent progress in understanding the role of the JAMs in leukocyte adhesion and migration to tentatively draw an integrated view of the homeostatic function of the JAMs within the hematopoietic system.


Assuntos
Moléculas de Adesão Juncional/imunologia , Leucócitos/imunologia , Junções Íntimas/imunologia , Animais , Movimento Celular/imunologia , Sistema Hematopoético/imunologia , Homeostase , Humanos
12.
Toxicol Pathol ; 40(3): 425-34, 2012 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-22215512

RESUMO

The immune and hematopoietic systems play an important role in the normal homeostasis of blood and blood cells and for immune responses to endogenous and exogenous processes and insults. In order to interpret histopathologic changes in the immune and hematopoietic systems, it is important to understand the normal anatomy and histology of the thymus, spleen, lymph nodes, bone marrow, and other tissues. The thymus, spleen, and lymph nodes can be categorized by anatomical compartments, each of which contributes to specific immune functions. Lesions may be diagnosed by interpretive or descriptive (semiquantitative) methods. The interpretation of these tissues by lesion in anatomical compartments should allow for better understanding of these reactions and more definitive pathologic findings. Proliferative lesions may be difficult to differentiate from lymphomas and leukemias. The use of immunohistochemistry, compartmental pathology, and methods for the evaluation of clonality will make interpretation easier.


Assuntos
Sistema Hematopoético/imunologia , Sistema Hematopoético/patologia , Tecido Linfoide/imunologia , Tecido Linfoide/patologia , Animais , Humanos , Hiperplasia , Transtornos Linfoproliferativos/imunologia , Transtornos Linfoproliferativos/patologia , Camundongos , Ratos
13.
Biomaterials ; 33(6): 1736-47, 2012 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-22136713

RESUMO

Here, we propose a collagen-based three-dimensional (3D) environment for hematopoietic stem and progenitor cells (HPC) with mesenchymal stem cells (MSC) derived either from bone marrow (BM) or umbilical cord (UC), to recapitulate the main components of the BM niche. Mechanisms described for HPC homeostasis were systematically analyzed in comparison to the conventional liquid HPC culture. The 3D-cultivation allows dissecting two sub-populations of HPC: (I) HPC in suspension above the collagen gel and (II) migratory HPC in the collagen fibres of the collagen gel. The different sites represent distinct microenvironments with significant impact on HPC fate. HPC in niche I (suspension) are proliferative and a dynamic culture containing HPC (CD34(+)/CD38(-)), maturing myeloid cells (CD38(+), CD13(+), CAE(+)) and natural killer (NK) cells (CD56(+)). In contrast, HPC in niche II showed clonal growth with significant high levels of the primitive CD34(+)/CD38(-) phenotype with starting myeloid (CD13(+), CAE(+)) differentiation, resembling the endosteal part of the BM niche. In contrast, UC-MSC are not adequate for HSC expansion as they significantly enhance HPC proliferation and lineage commitment. In conclusion, the 3D-culture system using collagen and BM-MSC enables HPC expansion and provides a potential platform to dissect regulatory mechanisms in hematopoiesis.


Assuntos
Técnicas de Cocultura/métodos , Células-Tronco Hematopoéticas/citologia , Células-Tronco Mesenquimais/citologia , ADP-Ribosil Ciclase 1/biossíntese , Antígenos CD34/biossíntese , Apoptose , Biotecnologia/métodos , Células da Medula Óssea/citologia , Antígenos CD13/biossíntese , Diferenciação Celular , Colágeno/química , Géis/química , Sistema Hematopoético/imunologia , Humanos , Fenótipo , Tecidos Suporte/química , Cordão Umbilical/citologia
14.
Nat Med ; 18(1): 135-42, 2011 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-22127134

RESUMO

The presentation pathways by which allogeneic peptides induce graft-versus-host disease (GVHD) are unclear. We developed a bone marrow transplant (BMT) system in mice whereby presentation of a processed recipient peptide within major histocompatibility complex (MHC) class II molecules could be spatially and temporally quantified. Whereas donor antigen presenting cells (APCs) could induce lethal acute GVHD via MHC class II, recipient APCs were 100-1,000 times more potent in this regard. After myeloablative irradiation, T cell activation and memory differentiation occurred in lymphoid organs independently of alloantigen. Unexpectedly, professional hematopoietic-derived recipient APCs within lymphoid organs had only a limited capacity to induce GVHD, and dendritic cells were not required. In contrast, nonhematopoietic recipient APCs within target organs induced universal GVHD mortality and promoted marked alloreactive donor T cell expansion within the gastrointestinal tract and inflammatory cytokine generation. These data challenge current paradigms, suggesting that experimental lethal acute GVHD can be induced by nonhematopoietic recipient APCs.


Assuntos
Células Apresentadoras de Antígenos/imunologia , Transplante de Medula Óssea/imunologia , Linfócitos T CD4-Positivos/imunologia , Doença Enxerto-Hospedeiro/imunologia , Antígenos de Histocompatibilidade Classe II/imunologia , Animais , Apresentação do Antígeno/imunologia , Células Apresentadoras de Antígenos/citologia , Citocinas/imunologia , Células Dendríticas/imunologia , Sistema Hematopoético/imunologia , Humanos , Ativação Linfocitária/imunologia , Camundongos , Camundongos Endogâmicos BALB C , Sítio Doador de Transplante , Transplante Homólogo
15.
Eur J Immunol ; 41(12): 3467-78, 2011 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-21928285

RESUMO

We previously identified a population of residual T(reg) cells following autologous hematopoietic stem transplantation (HSCT), that rapidly undergoes significant expansion in lymphopenic transplant recipients prior to repopulation by donor de novo derived T(reg) cells. These CD4(+) Foxp3(+) T cells provide protection from the development of autoimmune disease. Although ablative conditioning results in excess IL-7 and IL-15, IL-2 is typically not found at high levels following autologous HSCT. We therefore examined the role of these three STAT-5 signaling cytokines in the expansion of residual T(reg) cells after autologous HSCT. The present study found that the residual T(reg) cell population included surviving peripheral host Foxp3(+) CD4(+) T cells whose expansion was critically dependent on IL-2, which could be solely provided by surviving host cells. IL-7 was found to contribute to T(reg) cell homeostasis, however, not as a growth factor but rather for their persistence. In conjunction with this expansion, TCR spectratype analyses revealed that the residual host T(reg) -cell compartment differed from that present in non-conditioned healthy mice since the residual host Treg cells exhibit a limited TCR diversity. Collectively, these data indicate that the proliferation of T(reg) and T effector (T(eff) ) cells post-HSCT utilize separate pools of cytokines which has important implications regarding the development of clinical strategies to elicit the desired immune responses in patients post-transplant.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Sistema Hematopoético/imunologia , Interleucina-2/imunologia , Linfócitos T Reguladores/imunologia , Linfócitos T Reguladores/transplante , Animais , Linfócitos T CD4-Positivos/imunologia , Fatores de Transcrição Forkhead/imunologia , Sistema Hematopoético/citologia , Interleucina-2/genética , Interleucina-7/imunologia , Linfopenia/imunologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Receptores de Antígenos de Linfócitos T/imunologia , Subpopulações de Linfócitos T/imunologia , Timo/imunologia
16.
Trends Immunol ; 32(7): 321-7, 2011 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-21697012

RESUMO

Human hemato-lymphoid-system mice hold great promise for modeling and studying important human diseases in vivo, and to enable vaccine testing. Until now, several major limitations have restricted the utility of human hemato-lymphoid-system mice in translational research. Recently, however, significant advances have been made in improving these mice, based on the delivery of human cytokines to create a better environment for human cells in the mouse host. In this review, we discuss the various approaches with a particular focus on improving human hemato-lymphoid-system mice by human cytokine knock-in gene replacement.


Assuntos
Citocinas/imunologia , Sistema Hematopoético/imunologia , Tecido Linfoide/imunologia , Animais , Linhagem da Célula , Citocinas/genética , Técnicas de Introdução de Genes , Sistema Hematopoético/citologia , Humanos , Tecido Linfoide/citologia , Camundongos , Pesquisa Médica Translacional
17.
Brain Behav Immun ; 25 Suppl 1: S71-9, 2011 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-21195165

RESUMO

Alzheimer's disease (AD) is the most prevalent cause of dementia in humans. This disease is characterized by the presence of amyloid beta (Ab) deposits in the parenchyma (also known as amyloid plaques or senile plaques) and in the cerebral vasculature. Though Ab formation and deposits are strongly correlated with cognitive impairment, the mechanisms responsible for the synaptic dysfunctions and loss of neurons in AD remain largely unknown. Many studies have provided evidence that microglial cells are attracted to amyloid deposits both in human samples and in rodent transgenic models that develop this disease. We have recently found that blood-derived microglia and not their resident counterparts have the ability to eliminate amyloid deposits by a cell-specific phagocytic mechanism. These bone marrow-derived microglia have consequently a great therapeutic potential for AD patients. Molecular strategies aiming to improve their recruitment could lead to a new powerful tool for the elimination of toxic Ab and improve cognitive functions. However, numerous limitations have to be taken into consideration before recommending such a cellular therapy and these are discussed in the present review.


Assuntos
Doença de Alzheimer/terapia , Sistema Hematopoético/imunologia , Imunidade Inata/imunologia , Microglia/imunologia , Placa Amiloide/imunologia , Doença de Alzheimer/imunologia , Animais , Humanos , Camundongos , Camundongos Transgênicos
18.
Blood ; 117(4): 1146-55, 2011 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-21088134

RESUMO

We have recently reported that CD8(+) T-cell memory maintenance after immunization with recombinant human adenovirus type 5 (rHuAd5) is dependent upon persistent transgene expression beyond the peak of the response. In this report, we have further investigated the location and nature of the cell populations responsible for this sustained response. The draining lymph nodes were found to be important for primary expansion but not for memory maintenance, suggesting that antigen presentation through a nonlymphoid source was required. Using bone marrow chimeric mice, we determined that antigen presentation by nonhematopoietic antigen-presenting cells (APCs) was sufficient for maintenance of CD8(+) T-cell numbers. However, antigen presentation by this mechanism alone yielded a memory population that displayed alterations in phenotype, cytokine production and protective capacity, indicating that antigen presentation through both hematopoietic and nonhematopoietic APCs ultimately defines the memory CD8(+) T-cell response produced by rHuAd5. These results shed new light on the immunobiology of rHuAd5 vectors and provide evidence for a mechanism of CD8(+) T-cell expansion and memory maintenance that relies upon both hematopoietic and nonhematopoietic APCs.


Assuntos
Adenovírus Humanos/imunologia , Linfócitos T CD8-Positivos/imunologia , Imunização , Memória Imunológica/fisiologia , Vacinas Virais/imunologia , Animais , Apresentação do Antígeno/imunologia , Células Apresentadoras de Antígenos/imunologia , Vacinas Anticâncer/imunologia , Vacinas Anticâncer/uso terapêutico , Células Cultivadas , Feminino , Sistema Hematopoético/imunologia , Humanos , Imunização/métodos , Ativação Linfocitária/imunologia , Melanoma Experimental/imunologia , Melanoma Experimental/patologia , Melanoma Experimental/terapia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Transplante de Neoplasias , Terapia Viral Oncolítica/métodos , Vacinas Sintéticas/imunologia
19.
Histol Histopathol ; 26(2): 247-65, 2011 02.
Artigo em Inglês | MEDLINE | ID: mdl-21154238

RESUMO

Galectin-3 belongs to a family of highly conserved animal lectins characterized by their ability to recognize multiple N-acetyllactosamine sequences, which can be displayed on both N- and O-glycans on cell surface glycoconjugates. Although first identified in macrophages, galectin-3 (also called "Mac-2, εBP, CBP35 or L-29") has been found to be widely distributed in several tissues and developmental stages where, depending on its extracellular or intracellular localization, it can display a broad diversity of biological functions including immunomodulation, host-pathogen interactions, embryogenesis, angiogenesis, cell migration, wound healing and apoptosis. In spite of the existence of several reviews describing the multifunctional properties of galectin-3, an integrated view of the regulated expression of this glycan-binding protein in different normal tissues is lacking. Here we attempt to summarize and integrate available information on galectin-3 distribution in normal haematopoietic and non-haematopoietic tissues, mainly in adulthood, with only a brief reference to its expression during embryonic stages. In addition, given the multiplicity of biological roles attributed to this protein, a brief description of galectin-3 functions is also included. Understanding how galectin-3 is regulated in normal tissues will contribute to a rational design of approaches aimed at modulating galectin-3 expression and subcellular localization for experimental and therapeutic purposes.


Assuntos
Células da Medula Óssea/metabolismo , Galectina 3/metabolismo , Regulação da Expressão Gênica , Hematopoese/fisiologia , Sistema Hematopoético/metabolismo , Animais , Células da Medula Óssea/imunologia , Embrião de Mamíferos/metabolismo , Desenvolvimento Embrionário/fisiologia , Galectina 3/imunologia , Sistema Hematopoético/imunologia , Humanos , Imunomodulação/fisiologia , Camundongos , Camundongos Knockout
20.
Nat Rev Immunol ; 10(12): 813-25, 2010 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-21088682

RESUMO

T cells encounter their cognate antigens in specialized compartments of secondary lymphoid organs (SLOs). There, dendritic cells (DCs) present self and non-self antigens to T cells, and promote immunity or tolerance depending on the availability of danger signals. Resident stromal cells orchestrate the interaction between T cells and DCs by recruiting them to T cell zones and guiding their migration within SLOs. Recent studies have shown that SLO-resident stromal cells also have a crucial role in tolerance induction in the periphery. In this Review, we discuss the roles of SLO-resident DCs and stromal cells in shaping T cell responses.


Assuntos
Células Apresentadoras de Antígenos/imunologia , Sistema Hematopoético/imunologia , Tecido Linfoide/imunologia , Animais , Antígenos/imunologia , Movimento Celular/imunologia , Humanos , Tolerância Imunológica , Camundongos , Células Estromais/imunologia , Linfócitos T/imunologia
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