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1.
Nat Commun ; 11(1): 3798, 2020 07 30.
Artigo em Inglês | MEDLINE | ID: mdl-32732867

RESUMO

Blood vascular endothelial cells (BECs) control the immune response by regulating blood flow and immune cell recruitment in lymphoid tissues. However, the diversity of BEC and their origins during immune angiogenesis remain unclear. Here we profile transcriptomes of BEC from peripheral lymph nodes and map phenotypes to the vasculature. We identify multiple subsets, including a medullary venous population whose gene signature predicts a selective role in myeloid cell (vs lymphocyte) recruitment to the medulla, confirmed by videomicroscopy. We define five capillary subsets, including a capillary resident precursor (CRP) that displays stem cell and migratory gene signatures, and contributes to homeostatic BEC turnover and to neogenesis of high endothelium after immunization. Cell alignments show retention of developmental programs along trajectories from CRP to mature venous and arterial populations. Our single cell atlas provides a molecular roadmap of the lymph node blood vasculature and defines subset specialization for leukocyte recruitment and vascular homeostasis.


Assuntos
Células Endoteliais/citologia , Endotélio Vascular/citologia , Linfonodos/irrigação sanguínea , Linfócitos/imunologia , Células Mieloides/imunologia , Animais , Sequência de Bases , Movimento Celular/imunologia , Feminino , Perfilação da Expressão Gênica , Homeostase/imunologia , Inflamação/imunologia , Tecido Linfoide/imunologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Transgênicos , Análise de Sequência de RNA , Análise de Célula Única , Transcriptoma/genética
2.
Mol Immunol ; 124: 42-50, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32526556

RESUMO

CD8+ T cells are crucial for immunity against viral infections, including HIV. Several characteristics of CD8+ T cells, such as polyfunctionality and cytotoxicity, have been correlated with effective control of HIV. However, most of these correlates have been established in the peripheral blood. Meanwhile, HIV primarily replicates in lymphoid tissues. Therefore, it is unclear which aspects of CD8+ T cell biology are shared and which are different between blood and lymphoid tissues in the context of HIV infection. In this review, we will recapitulate the latest advancements of our knowledge on lymphoid tissue CD8+ T cells during HIV infection and discuss the insights these advancements might provide for the development of a HIV cure.


Assuntos
Linfócitos T CD8-Positivos/imunologia , Infecções por HIV/imunologia , Tecido Linfoide/imunologia , Humanos
3.
Nihon Shokakibyo Gakkai Zasshi ; 117(5): 413-420, 2020.
Artigo em Japonês | MEDLINE | ID: mdl-32389913

RESUMO

A 15-mm whitish, depressed lesion was observed in the stomach of a 39-year-old using screening esophagogastroduodenoscopy. The lesion had grown to a size of 40mm and had a cobblestone-like appearance at an 11-year endoscopic follow-up. Using endoscopic submucosal dissection (ESD) as a diagnostic therapy, gastric mucosa-associated lymphoid tissue (MALT) lymphoma with MALT translocation gene 1 without Helicobacter pylori infection was detected. Although the patient did not undergo additional treatments, he remained alive without for recurrence 5 years after ESD.


Assuntos
Ressecção Endoscópica de Mucosa , Infecções por Helicobacter , Helicobacter pylori , Linfoma de Zona Marginal Tipo Células B , Neoplasias Gástricas , Adulto , Mucosa Gástrica , Humanos , Tecido Linfoide , Masculino , Recidiva Local de Neoplasia
4.
Bull Cancer ; 107(7-8): 813-822, 2020.
Artigo em Francês | MEDLINE | ID: mdl-32451070

RESUMO

Radiation induced lymphopenia is frequent and can be severe and durable. Although lymphocytes have long been known as highly radiosensitive cells, it is poorly characterized. Radiation-induced lymphopenia seems to affect lymphocyte subpopulations differently and seems to be influenced by radiation modalities. The depth and duration of lymphopenia depend on the location of the irradiation and the volumes of treatment. Importantly, radiation-induced lymphopenia has been associated with poorer prognosis in several tumor types. The knowledge about radiation-induced lymphopenia might lead to a rethinking of the modalities of radiotherapy and new approaches to restore lymphocytes counts.


Assuntos
Linfopenia/etiologia , Linfopenia/terapia , Linfócitos T/efeitos da radiação , Humanos , Subpopulações de Linfócitos/efeitos da radiação , Tecido Linfoide/efeitos da radiação , Neoplasias/sangue , Neoplasias/imunologia , Prognóstico , Tolerância a Radiação , Radioterapia/efeitos adversos , Radioterapia/métodos , Linfócitos T/fisiologia
5.
Avian Dis ; 64(1): 69-79, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32267127

RESUMO

The development of immunocompetence in chicks after hatching is not fully understood. However, detailed knowledge of immunocompetence and maturation processes in day-old chicks (DOCs) and juvenile chickens (Gallus gallus domesticus) is necessary to implement enhanced immunization strategies. For viral diseases, this especially includes the development of cellular immunity focusing on T-cell-dependent responses. In the current study, we investigated T-cell subsets in blood and lymphoid tissues of 1-to-21-day-old chickens concerning their cellular composition and localization. We detected an increase of T-cell frequencies in blood and spleen and a shift of the CD8α dimer expression toward a CD8αß expression on the surface of T cells with increasing age. A relocalization of lymphocytes into antigen presentation structures within the spleen was affirmed. In addition, changes in basal messenger RNA (mRNA) level, with increasing IL2 and IFNγ mRNA levels at different ages were measured. These detected changes suggest an improved T-cell-dependent antiviral response with increasing age in chickens. To confirm this finding on a functional level, we conducted a transfer experiment: adult and, as a negative control, neonatal naïve lymphocytes were transferred into DOCs. Afterward, the protection induced by these transferred cells was verified by a sublethal infection by using a highly pathogenic avian influenza virus with neuraminidase deletion, H5Ndel. Previous experiments have shown that adult animals survive infection with this virus strain, while naïve DOCs show severe symptoms or even die. As a result, the transfer of adult, but not neonatal lymphocytes, confers protection to DOCs against the infection, demonstrating functional differences in lymphocytes from chicks of different ages. Collectively, these data reveal the inability of chicks to mount an effective, cellular antiviral response in the first 3 wk of life. Therefore, we propose that the observed maturation of both the innate and the adaptive arms of the immune system early in development is mandatory for controlling influenza infection in chickens, as well as for an effective vaccination with replication-competent viral vaccine strains.


Assuntos
Sangue/imunologia , Galinhas/imunologia , Imunidade Celular , Imunocompetência , Virus da Influenza A Subtipo H5N1/imunologia , Tecido Linfoide/imunologia , Linfócitos T/fisiologia , Fatores Etários , Animais , Feminino , Masculino
6.
Immunity ; 52(3): 557-570.e6, 2020 03 17.
Artigo em Inglês | MEDLINE | ID: mdl-32160523

RESUMO

The intestine contains some of the most diverse and complex immune compartments in the body. Here we describe a method for isolating human gut-associated lymphoid tissues (GALTs) that allows unprecedented profiling of the adaptive immune system in submucosal and mucosal isolated lymphoid follicles (SM-ILFs and M-ILFs, respectively) as well as in GALT-free intestinal lamina propria (LP). SM-ILF and M-ILF showed distinct patterns of distribution along the length of the intestine, were linked to the systemic circulation through MAdCAM-1+ high endothelial venules and efferent lymphatics, and had immune profiles consistent with immune-inductive sites. IgA sequencing analysis indicated that human ILFs are sites where intestinal adaptive immune responses are initiated in an anatomically restricted manner. Our findings position ILFs as key inductive hubs for regional immunity in the human intestine, and the methods presented will allow future assessment of these compartments in health and disease.


Assuntos
Imunidade Adaptativa/imunologia , Imunidade nas Mucosas/imunologia , Mucosa Intestinal/imunologia , Intestinos/imunologia , Tecido Linfoide/imunologia , Imunidade Adaptativa/genética , Animais , Citometria de Fluxo , Mucosa Gástrica/imunologia , Mucosa Gástrica/metabolismo , Mucosa Gástrica/ultraestrutura , Humanos , Imunidade nas Mucosas/genética , Imunoglobulina A/genética , Imunoglobulina A/imunologia , Imunoglobulina M/genética , Imunoglobulina M/imunologia , Mucosa Intestinal/metabolismo , Mucosa Intestinal/ultraestrutura , Intestinos/ultraestrutura , Linfócitos/imunologia , Linfócitos/metabolismo , Tecido Linfoide/metabolismo , Tecido Linfoide/ultraestrutura , Microscopia Confocal , Microscopia Eletrônica de Varredura , Nódulos Linfáticos Agregados/imunologia , Nódulos Linfáticos Agregados/metabolismo , Nódulos Linfáticos Agregados/ultraestrutura , Análise de Sequência de DNA
7.
Immunity ; 52(3): 452-463, 2020 03 17.
Artigo em Inglês | MEDLINE | ID: mdl-32187516

RESUMO

The intestines have the essential but challenging mission of absorbing nutrients, restricting damage from food-derived toxins, promoting colonization by symbionts, and expelling pathogens. These processes are often incompatible with each other and must therefore be prioritized in view of the most crucial contemporary needs of the host. Recent work has shown that tissue-resident innate lymphoid cells (ILCs) constitute a central sensory module allowing adaptation of intestinal organ function to changing environmental input. Here, we propose a conceptual framework positing that the various types of ILC act in distinct modules with intestinal epithelial cells, collectively safeguarding organ function. Such homeostasis-promoting circuitry has high potential to be plumbed for new therapeutic approaches to the treatment of immune-mediated inflammatory diseases.


Assuntos
Células Epiteliais/imunologia , Homeostase/imunologia , Imunidade Inata/imunologia , Mucosa Intestinal/imunologia , Linfócitos/imunologia , Animais , Citocinas/imunologia , Citocinas/metabolismo , Células Epiteliais/metabolismo , Humanos , Mucosa Intestinal/citologia , Mucosa Intestinal/metabolismo , Linfócitos/metabolismo , Tecido Linfoide/citologia , Tecido Linfoide/imunologia , Tecido Linfoide/metabolismo , Modelos Imunológicos
8.
PLoS One ; 15(2): e0228484, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32017809

RESUMO

Rhesus macaque (RM) rhadinovirus (RRV) is a simian gamma-2 herpesvirus closely related to human Kaposi's sarcoma-associated herpesvirus (KSHV). RRV is associated with the development of diseases in simian immunodeficiency virus (SIV) co-infected RM that resemble KSHV-associated pathologies observed in HIV-infected humans, including B cell lymphoproliferative disorders (LPD) and lymphoma. Importantly, how de novo KSHV infection affects the expression of host genes in humans, and how these alterations in gene expression affect viral replication, latency, and disease is unknown. The utility of the RRV/RM infection model provides a novel approach to address these questions in vivo, and utilizing the RRV bacterial artificial chromosome (BAC) system, the effects of specific viral genes on host gene expression patterns can also be explored. To gain insight into the effects of RRV infection on global host gene expression patterns in vivo, and to simultaneously assess the contributions of the immune inhibitory viral CD200 (vCD200) molecule to host gene regulation, RNA-seq was performed on pre- and post-infection lymph node (LN) biopsy samples from RM infected with either BAC-derived WT (n = 4) or vCD200 mutant RRV (n = 4). A variety of genes were identified as being altered in LN tissue samples due to RRV infection, including cancer-associated genes activation-induced cytidine deaminase (AICDA), glypican-1 (GPC1), CX3C chemokine receptor 1 (CX3CR1), and Ras dexamethasone-induced 1 (RasD1). Further analyses also indicate that GPC1 may be associated with lymphomagenesis. Finally, comparison of infection groups identified the differential expression of host gene thioredoxin interacting protein (TXNIP), suggesting a possible mechanism by which vCD200 negatively affects RRV viral loads in vivo.


Assuntos
Perfilação da Expressão Gênica/veterinária , Infecções por Herpesviridae/veterinária , Rhadinovirus/patogenicidade , Infecções Tumorais por Vírus/veterinária , Animais , Receptor 1 de Quimiocina CX3C/genética , Transformação Celular Neoplásica/genética , Citidina Desaminase/genética , Regulação Neoplásica da Expressão Gênica , Glipicanas/genética , Infecções por Herpesviridae/genética , Tecido Linfoide/metabolismo , Macaca mulatta , Análise de Sequência de RNA/veterinária , Infecções Tumorais por Vírus/genética , Latência Viral , Replicação Viral , Proteínas ras/genética
9.
PLoS One ; 15(2): e0228463, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32027689

RESUMO

Infection with Brucella abortus causes contagious zoonosis, brucellosis, and leads to abortion in animals and chronic illness in humans. Chitosan nanoparticles (CNs), biocompatible and nontoxic polymers, acts as a mucosal adjuvant. In our previous study, B. abortus malate dehydrogenase (Mdh) was loaded in CNs, and it induced high production of pro-inflammatory cytokines in THP-1 cells and systemic IgA in BALB/C mice. In this study, the time-series gene expression analysis of nasal-associated lymphoid tissue (NALT) was performed to identify the mechanism by which Mdh affect the target site of nasal immunization. We showed that intranasal immunization of CNs-Mdh reduced cell viability of epithelial cells and muscle cells at first 1 h, then induced cellular movement of immune cells such as granulocytes, neutrophils and lymphocytes at 6h, and activated IL-6 signaling pathway at 12h within NALT. These activation of immune cells also promoted signaling pathway for high-mobility group box 1 protein (HMGB1), followed by the maturation of DCs required for mucosal immunity. The CNs also triggered the response to other organism and inflammatory response, showing it is immune-enhancing adjuvant. The ELISA showed that significant production of specific IgA was detected in the fecal excretions and genital secretions from the CNs-Mdh-immunized group after 2 weeks-post immunization. Collectively, these results suggest that B. abortus Mdh-loaded CNs triggers activation of HMGB1, IL-6 and DCs maturation signaling within NALT and induce production of systemic IgG and IgA.


Assuntos
Formação de Anticorpos/fisiologia , Brucella abortus/imunologia , Brucelose/prevenção & controle , Imunização/métodos , Tecido Linfoide/imunologia , Malato Desidrogenase/imunologia , Administração Intranasal , Animais , Formação de Anticorpos/efeitos dos fármacos , Brucella abortus/metabolismo , Brucelose/imunologia , Quitosana/administração & dosagem , Quitosana/química , Quitosana/imunologia , Quitosana/farmacologia , Portadores de Fármacos/administração & dosagem , Portadores de Fármacos/química , Feminino , Imunidade nas Mucosas/efeitos dos fármacos , Imunogenicidade da Vacina , Tecido Linfoide/efeitos dos fármacos , Malato Desidrogenase/administração & dosagem , Malato Desidrogenase/metabolismo , Malato Desidrogenase/farmacologia , Camundongos , Camundongos Endogâmicos BALB C , Nanopartículas/administração & dosagem , Mucosa Nasal/efeitos dos fármacos , Mucosa Nasal/imunologia
10.
Medicine (Baltimore) ; 99(6): e18926, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32028400

RESUMO

Lymphoid follicles/aggregates in gastric biopsies have been traditionally linked to Helicobacter pylori gastritis, and less commonly to other inflammatory and neoplastic conditions. The frequency of such aggregates in normal stomachs has yet to be adequately evaluated. This is especially relevant when it comes to diagnosing non-specific chronic gastritis in biopsy specimens with chronic inflammation but no evidence of H pylori infection. Sleeve gastrectomies represent an opportunity to study adequately preserved gastric mucosa in patients who are otherwise asymptomatic and lack a history of gastric disease.To study sleeve gastrectomy specimens to quantify the amount of lymphoid follicles/aggregates and lymphocytic infiltration in normal stomachs.Sixty-eight bariatric sleeve gastrectomies and 13 control specimens from Whipple resections were examined for multiple histologic features including type, quantity, and distribution of chronic inflammation and lymphoid follicles/aggregates. Presence of H pylori was documented by both Hematoxylin and eosin-stained (H&E) and immunohistochemistry (IHC). Clinical information including age, sex, medication intake, prior endoscopy, and/or H pylori infection was recorded. The patient population was divided in 2 groups, H pylori negative versus H pylori positive, and statistical analysis was performed by a biostatistician.Two hundred sixty three fundic sections from 68 bariatric patients were examined. Fifty three patients were found to be H pylori-negative, compared with 15 who were positive for H pylori. Among the H pylori-negative group, the average number of lymphoid aggregates was 3.33, compared with an average of 6.26 in the H pylori positive group (the difference was statistically significant with a P-value of .008). The average number of plasma cells per high power field was 2.15 in the H pylori negative group, compared and average of 5.07 in the H pylori positive group (the difference was also statistically significant with a P-value <.001). Clinically, 10 of the 53 H pylori-negative patients had esophagogastroduodenoscopy (EGD) that showed endoscopic mild non-erosive gastric erythema. The remaining had no documentation of symptoms or medication intake, including Non-steroidal anti-inflammatory drugs (NSAIDs) and Proton Pump Inhibitors (PPI).Our results suggest that the presence of lymphoid aggregates and plasma cells infiltration can be a normal finding in otherwise normal gastric mucosa, though more pronounced in H pylori infected patients.


Assuntos
Mucosa Gástrica/patologia , Gastrite/patologia , Infecções por Helicobacter/patologia , Helicobacter pylori/isolamento & purificação , Tecido Linfoide/citologia , Plasmócitos/citologia , Estudos de Casos e Controles , Feminino , Gastrectomia , Gastrite/diagnóstico , Humanos , Masculino
11.
PLoS One ; 15(2): e0228327, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32059005

RESUMO

Chronic wasting disease (CWD) continues to spread or be recognized in the United States, Canada, and Europe. CWD is diagnosed by demonstration of the causative misfolded prion protein (PrPCWD) in either brain or lymphoid tissue using immunodetection methods, with immunohistochemistry (IHC) recognized as the gold standard. In recent years, in vitro amplification assays have been developed that can detect CWD prion seeding activity in tissues, excreta, and body fluids of affected cervids. These methods potentially offer earlier and more facile detection of CWD, both pre- and post-mortem. Here we provide a longitudinal profile of CWD infection progression, as assessed by both real-time quaking-induced conversion (RT-QuIC) and IHC on serial biopsies of mucosal lymphoid tissues of white-tailed deer orally exposed to low doses of CWD prions. We report that detection of CWD infection by RT-QuIC preceded that by IHC in both tonsil and recto-anal lymphoid tissue (RAMALT) in 14 of 19 deer (74%). Of the 322 biopsy samples collected in post-exposure longitudinal monitoring, positive RT-QuIC results were obtained for 146 samples, 91 of which (62%) were concurrently also IHC-positive. The lower frequency of IHC positivity was manifest most in the earlier post-exposure periods and in biopsies in which lymphoid follicles were not detected. For all deer in which RT-QuIC seeding activity was detected in a tonsil or RAMALT biopsy, PrPCWD was subsequently or concurrently detected by IHC. Overall, this study (a) provides a longitudinal profile of CWD infection in deer after low yet infectious oral prion exposure; (b) illustrates the value of RT-QuIC for sensitive detection of CWD; and (c) demonstrates an ultimate high degree of correlation between RT-QuIC and IHC positivity as CWD infection progresses.


Assuntos
Imuno-Histoquímica , Técnicas de Amplificação de Ácido Nucleico/métodos , Doença de Emaciação Crônica/patologia , Administração Oral , Animais , Cervos , Progressão da Doença , Estudos Longitudinais , Tecido Linfoide/metabolismo , Tecido Linfoide/patologia , Tonsila Palatina/metabolismo , Tonsila Palatina/patologia , Proteínas Priônicas/genética , Proteínas Priônicas/metabolismo , Príons/administração & dosagem , Doença de Emaciação Crônica/metabolismo
12.
Gene ; 739: 144496, 2020 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-32088242

RESUMO

Early larval developmental stages of fish are highly susceptible to opportunistic pathogens until the complete maturation of the lymphoid organs. Knowledge of the expression pattern of important markers of adaptive immune system during the ontogenetic development is essential before vaccinating the fish. In the present study, Pterophyllum scalare (angelfish) was taken to explore the relative expression profile of developmental markers of adaptive immunity, recombination activating gene-2 (RAG-2) and immunoglobulin M (IgM). The fishes were bred and early developmental stages (0-45 days post-hatched) were used to assess the expression profile. The genes, RAG-2 and IgM were cloned and sequenced with the base pair lengths of 1958 bp and 225 bp respectively. The mRNA expression of RAG-2 appeared at insignificant level at the first day of hatching, but the expression was significantly increased from 24 dph (days post-hatching) onwards and reached its peak at 27 dph. The results proved that the maturation of lymphoid organs was completed at 27 dph as the respective protein is involved in the V(D)J recombination, important for the maturation of lymphoid organs. A similar trend was also observed in the mRNA transcript levels of IgM gene and a significantly high expression was detected from 27 dph onwards. The present study suggested that the suitable time for vaccination in P. scalare could be taken at 27 dph, as the maturation and development of lymphoid organs is completed thus helps in stimulating the adaptive response of immunity against any pathogen.


Assuntos
Imunidade Adaptativa/genética , Ciclídeos/genética , Proteínas de Ligação a DNA/imunologia , Vacinação/veterinária , Animais , Ciclídeos/imunologia , Clonagem Molecular , Proteínas de Ligação a DNA/genética , Proteínas de Peixes/genética , Proteínas de Peixes/imunologia , Imunoglobulina M/genética , Imunoglobulina M/imunologia , Rim/imunologia , Tecido Linfoide/imunologia , Baço/imunologia
13.
PLoS One ; 15(2): e0229743, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32106280

RESUMO

Thymocyte selection-associated high-mobility group box (TOX) is a DNA-binding factor that is able to regulate transcription by modifying local chromatin structure and modulating the formation of multi-protein complexes. TOX has multiple roles in the development of the adaptive immune system including development of CD4 T cells, NK cells and lymph node organogenesis. However very few antibodies recognizing this molecule have been reported and no extensive study of the expression of TOX in reactive and neoplastic lymphoid tissue has been performed to date. In the present study, we have investigated TOX expression in normal and neoplastic lymphoid tissues using a novel rat monoclonal antibody that recognizes its target molecule in paraffin-embedded tissue sections. A large series of normal tissues and B- and T-cell lymphomas was studied, using whole sections and tissue microarrays. We found that the majority of precursor B/T lymphoblastic, follicular and diffuse large B-cell lymphomas, nodular lymphocyte-predominant Hodgkin lymphomas and angioimmunoblastic T-cell lymphomas strongly expressed the TOX protein. Burkitt and mantle cell lymphomas showed TOX expression in a small percentage of cases. TOX was not found in the majority of chronic lymphocytic leukemia, myelomas, marginal zone lymphomas and classical Hodgkin lymphomas. In conclusion, we describe for the first time the expression of TOX in normal and neoplastic lymphoid tissues. The co-expression of TOX and PD-1 identified in normal and neoplastic T cells is consistent with recent studies identifying TOX as a critical regulator of T-cell exhaustion and a potential immunotherapy target. Its differential expression may be of diagnostic relevance in the differential diagnosis of follicular lymphoma, the identification of the phenotype of diffuse large B-cell lymphoma and the recognition of peripheral T-cell lymphoma with a follicular helper T phenotype.


Assuntos
Anticorpos Monoclonais Murinos/imunologia , Subpopulações de Linfócitos B/imunologia , Proteínas de Grupo de Alta Mobilidade/imunologia , Subpopulações de Linfócitos T/imunologia , Animais , Especificidade de Anticorpos , Subpopulações de Linfócitos B/metabolismo , Subpopulações de Linfócitos B/patologia , Linhagem Celular Tumoral , Feminino , Expressão Gênica , Proteínas de Grupo de Alta Mobilidade/genética , Proteínas de Grupo de Alta Mobilidade/metabolismo , Humanos , Tecido Linfoide/imunologia , Tecido Linfoide/metabolismo , Linfoma de Células B/imunologia , Linfoma de Células B/metabolismo , Linfoma de Células B/patologia , Linfoma de Células T/imunologia , Linfoma de Células T/metabolismo , Linfoma de Células T/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos , Ratos Wistar , Subpopulações de Linfócitos T/metabolismo , Subpopulações de Linfócitos T/patologia
14.
Proc Natl Acad Sci U S A ; 117(8): 4292-4299, 2020 02 25.
Artigo em Inglês | MEDLINE | ID: mdl-32034098

RESUMO

The migratory patterns of virus-specific CD8 T cells during chronic viral infection are not well understood. To address this issue, we have done parabiosis experiments during chronic lymphocytic choriomeningitis virus (LCMV) infection of mice. We found that despite the high frequency of virus-specific CD8 T cells in both lymphoid and nonlymphoid tissues there was minimal migration of virus-specific CD8 T cells between the chronically infected conjoined parabiont mice. This was in contrast to parabionts between mice that had undergone an acute LCMV infection where virus-specific CD8 T cells established equilibrium demonstrating circulation of memory T cells generated after viral clearance. We have identified a population of PD-1+ TCF1+CXCR5+Tim-3- stemlike virus-specific CD8 T cells that reside in lymphoid tissues and act as resource cells for maintaining the T cell response during chronic infection. These are the cells that proliferate and give rise to the more terminally differentiated PD-1+ CXCR5-Tim-3+ CD8 T cells. Both the stemlike CD8 T cells and their terminally differentiated progeny showed minimal migration during chronic infection and the few LCMV-specific CD8 T cells that were present in circulation were the recently emerging progeny from the stemlike CD8 T cells. The PD-1+ TCF1+CXCR5+ stemlike CD8 T cells were truly resident in lymphoid tissues and did not circulate in the blood. We propose that this residency in specialized niches within lymphoid tissues is a key aspect of their biology and is essential for maintaining their quiescence and stemlike program under conditions of a chronic viral infection.


Assuntos
Linfócitos T CD8-Positivos/imunologia , Coriomeningite Linfocítica/imunologia , Vírus da Coriomeningite Linfocítica/fisiologia , Tecido Linfoide/imunologia , Receptor de Morte Celular Programada 1/imunologia , Animais , Feminino , Receptor Celular 2 do Vírus da Hepatite A/genética , Receptor Celular 2 do Vírus da Hepatite A/imunologia , Humanos , Memória Imunológica , Coriomeningite Linfocítica/genética , Coriomeningite Linfocítica/virologia , Vírus da Coriomeningite Linfocítica/genética , Tecido Linfoide/virologia , Camundongos , Camundongos Endogâmicos C57BL , Receptor de Morte Celular Programada 1/genética , Receptores CXCR5/genética , Receptores CXCR5/imunologia
15.
PLoS Comput Biol ; 16(2): e1007385, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-32084130

RESUMO

Our aim is to complement observer-dependent approaches of immune cell evaluation in microscopy images with reproducible measures for spatial composition of lymphocytic infiltrates. Analyzing such patterns of inflammation is becoming increasingly important for therapeutic decisions, for example in transplantation medicine or cancer immunology. We developed a graph-based assessment of lymphocyte clustering in full whole slide images. Based on cell coordinates detected in the full image, a Delaunay triangulation and distance criteria are used to build neighborhood graphs. The composition of nodes and edges are used for classification, e.g. using a support vector machine. We describe the variability of these infiltrates on CD3/CD20 duplex staining in renal biopsies of long-term functioning allografts, in breast cancer cases, and in lung tissue of cystic fibrosis patients. The assessment includes automated cell detection, identification of regions of interest, and classification of lymphocytic clusters according to their degree of organization. We propose a neighborhood feature which considers the occurrence of edges with a certain type in the graph to distinguish between phenotypically different immune infiltrates. Our work addresses a medical need and provides a scalable framework that can be easily adjusted to the requirements of different research questions.


Assuntos
Tecido Linfoide/anatomia & histologia , Análise de Célula Única , Neoplasias da Mama/patologia , Feminino , Humanos , Máquina de Vetores de Suporte
16.
Vet Res ; 51(1): 19, 2020 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-32093775

RESUMO

Marek's disease (MD) is a contagious disease of domestic chickens caused by MD viruses. MD has been controlled primarily by vaccinations, yet sporadic outbreaks of MD take place worldwide. Commonly used MD vaccines include HVT, SB-1 and CVI988/Rispens and their efficacies are reportedly dependent of multiple factors including host genetics. Our previous studies showed protective efficacy of a MD vaccine can differ drastically from one chicken line to the next. Advanced understanding on the underlying genetic and epigenetic factors that modulate vaccine efficacy would greatly improve the strategy in design and development of more potent vaccines. Two highly inbred lines of White Leghorn were inoculated with HVT and CVI988/Rispens. Bursa samples were taken 26 days post-vaccination and subjected to small RNA sequencing analysis to profile microRNAs (miRNA). A total of 589 and 519 miRNAs was identified in one line, known as line 63, 490 and 630 miRNAs were identified in the other, known as line 72, in response to HVT or CVI988/Rispens inoculation, respectively. HVT and CVI988/Rispens induced mutually exclusive 4 and 13 differentially expressed (DE) miRNAs in line 63 birds in contrast to a non-vaccinated group of the same line. HVT failed to induce any DE miRNA and CVI988/Rispens induced a single DE miRNA in line 72 birds. Thousands of target genes for the DE miRNAs were predicted, which were enriched in a variety of gene ontology terms and pathways. This finding suggests the epigenetic factor, microRNA, is highly likely involved in modulating vaccine protective efficacy in chicken.


Assuntos
Bolsa de Fabricius/metabolismo , Galinhas/imunologia , Regulação da Expressão Gênica , Tecido Linfoide/metabolismo , Vacinas contra Doença de Marek/metabolismo , MicroRNAs/genética , Animais , Bolsa de Fabricius/imunologia , Tecido Linfoide/imunologia , Vacinas contra Doença de Marek/administração & dosagem , MicroRNAs/metabolismo
17.
Cell Immunol ; 349: 104048, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32014271

RESUMO

NFAT2 activity was shown to be of critical importance in B cell receptor signaling, development and proliferation; however its role in B cell development in the periphery is still not completely understood. We confirmed that NFAT2 deletion leads to impaired B1 B cell development, supported by our finding of limited B1 progenitors in the bone marrow and spleen of NFAT2 deficient mice. Moreover, we show for the first time that loss of NFAT2 increases immature B cells in particular transitional T2 and T3 as well as mature follicular B cells while marginal zone B cells are decreased. We further demonstrate that NFAT2 regulates the expression of B220, CD23, CD38, IgM/IgD and ZAP70 in murine B cells. In vivo analyses revealed decreased proliferation and increased apoptosis of NFAT2 deficient B cells. In summary, this study provides an extensive analysis of the role of NFAT2 in peripheral B lymphocyte development.


Assuntos
Subpopulações de Linfócitos B/citologia , Linfopoese/fisiologia , Fatores de Transcrição NFATC/deficiência , Animais , Antígenos de Diferenciação de Linfócitos B/análise , Subpopulações de Linfócitos B/metabolismo , Feminino , Regulação da Expressão Gênica no Desenvolvimento , Técnicas de Inativação de Genes , Genes Letais , Heterozigoto , Imunoglobulina D/biossíntese , Imunoglobulina D/genética , Imunoglobulina M/biossíntese , Imunoglobulina M/genética , Antígenos Comuns de Leucócito/biossíntese , Antígenos Comuns de Leucócito/genética , Ativação Linfocitária , Tecido Linfoide/crescimento & desenvolvimento , Tecido Linfoide/patologia , Linfopoese/genética , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Fatores de Transcrição NFATC/fisiologia , Especificidade de Órgãos , Organismos Livres de Patógenos Específicos
18.
Mymensingh Med J ; 29(1): 92-96, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31915342

RESUMO

A cross sectional descriptive study was performed on 40 postmortem vermiform appendix (male 24 and female 16) to find out the diameter of lymphoid follicle of vermiform appendix of Bangladeshi people. The specimens were collected from autopsy laboratory of the Department of Forensic Medicine, Mymensingh Medical College, Mymensingh, Bangladesh by purposive sampling technique and were divided into four age groups. They were Group A (upto 20 years), Group B (21 to 40 years), Group C (41 to 60 years) and Group D (above 60 years). For this purpose, about 3mm long of whole thickness transverse section was taken from the middle of the vermiform appendix and thus the permanent slides were made for microscopic examination. To measure the diameter of the lymphoid follicle two measurements were taken. One was taken at the maximum diameter and another was perpendicular to it by ocular micrometer. Diameter of one largest and one smallest lymphoid follicles were measured and find out the mean diameter of lymphoid follicle between them. Diameter of lymphoid follicle = (Maximum transverse diameter + perpendicular diameter) /2. All data were recorded in the predesigned data sheet, analyzed by SPSS program (version 21, 2012) and compared with the findings of other national and international studies and standard text books. It was observed that diameter of lymphoid follicle of vermiform appendix gradually decreased as age advanced. The mean±SD diameter of lymphoid follicle was 580.31±37.07, 545.58±38.37, 485.68±40.20 and 428.12±68.41µm in Group A, B, C and D respectively. Statistical analysis shows that the mean differences of diameter of lymphoid follicle between A&B, C&D were statistically non significant at p= or >0.05 level, difference between Group B&C was statistically moderately significant at p<0.01 level and differences between Group A&C, B&D, A&D were statistically highly significant at p<0.001 level. Mean diameter of lymphoid follicle of vermiform appendix in male was higher (584.30±12.65µm in Group A, 549.42±38.36µm in Group B, 487.38±39.91µm in Group C, 430.68±70.30µm in Group D) than in female (576.31±53.77µm in Group A, 536.61±45.14µm in Group B, 483.14±46.68µm in Group C, 424.28±75.95µm in Group D) but mean difference between sexes in the different groups was statistically non significant at p=or >0.05 level. The present study will help to increase the information pool on the diameter of lymphoid follicle of vermiform appendix of Bangladeshi people.


Assuntos
Apêndice , Autopsia/métodos , Tecido Linfoide , Adulto , Fatores Etários , Idoso , Apêndice/anatomia & histologia , Apêndice/patologia , Grupo com Ancestrais do Continente Asiático , Bangladesh , Cadáver , Estudos Transversais , Grupos Étnicos , Feminino , Humanos , Tecido Linfoide/anatomia & histologia , Tecido Linfoide/patologia , Masculino , Pessoa de Meia-Idade , Fatores Sexuais , Adulto Jovem
20.
PLoS One ; 15(1): e0227732, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31929592

RESUMO

The ocular surface of the white domestic pig (Sus scrofa domestica) is used as a helpful model of the human ocular surface; however, a complete histological description has yet to be published. In this work, we studied porcine eyeballs with intact eyelids to describe and characterize the different structures that form the ocular surface, including the cornea and conjunctiva that covers the bulbar sclera, tarsi, and the nictitating membrane. We determined the distribution of goblet cells of different types over the conjunctiva and analyzed the conjunctival-associated lymphoid tissue (CALT). Porcine eyeballs were obtained from a local slaughterhouse, fixed, processed, and embedded in paraffin blocks. Tissue sections (4 µm) were stained with hematoxylin/eosin, Alcian blue/Periodic Acid Schiff, and Giemsa. Slides were also stained with lectins from Arachis hypogaea (PNA) and Helix pomatia (HPA) agglutinins and immunostained with rabbit anti-CD3. We found that the porcine cornea was composed of 6-8 epithelial cell layers, stroma, Descemet's membrane, and an endothelial monolayer. The total corneal thickness was 1131.0±87.5 µm (mean±standard error of the mean) in the center and increased to 1496.9±138.2 µm at the limbus. The goblet cell density was 71.25±12.29 cells/mm, ranging from the highest density (113.04±37.21 cells/mm) in the lower palpebral conjunctiva to the lowest density (12.69±4.29 cells/mm) in the bulbar conjunctiva. The CALT was distributed in the form of intraepithelial lymphocytes and subepithelial diffuse lymphoid tissue. Lenticular-shaped lymphoid follicles, about 8 per histological section, were also present within the conjunctival areas. In conclusion, we demonstrated that the analyzed porcine ocular structures are similar to those of humans, confirming the potential usefulness of pig eyes to study ocular surface physiology and pathophysiology.


Assuntos
Olho/ultraestrutura , Sus scrofa , Animais , Túnica Conjuntiva/citologia , Túnica Conjuntiva/ultraestrutura , Córnea/ultraestrutura , Células Caliciformes/ultraestrutura , Limbo da Córnea/ultraestrutura , Tecido Linfoide/ultraestrutura , Glândulas Tarsais/ultraestrutura , Coloração e Rotulagem/métodos , Sus scrofa/anatomia & histologia
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