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[PMID]:29184964
[Au] Autor:Costa C; Di Nauta A; Rittà M; Sinesi F; Bianco G; Sidoti F; Solidoro P; Cavallo R
[Ad] Endereço:Microbiology and Virology Unit, Laboratory of Virology.
[Ti] Título:Development of an EliSPOT assay for HSV-1 and clinical validation in lung transplant patients.
[So] Source:New Microbiol;40(4):251-257, 2017 Oct.
[Is] ISSN:1121-7138
[Cp] País de publicação:Italy
[La] Idioma:eng
[Ab] Resumo:Cellular immunity plays a major role in the control of HSV-1 infection/reactivation with a potential impact on the clinical-therapeutic management of immunocompromised patients, such as transplant recipients. Herein, we quantitatively evaluated T-cell response directed at HSV-1 by a newly developed IFN-γ EliSPOT assay in 53 patients (including 45 lung transplant recipients and eight subjects in waiting list). Overall, 62.2% of transplant patients and 62.5% of subjects on the waiting list showed a response to HSV-1 with no significant difference in the level of virus-specific cellular immunity. Response tended to be lower in the first three months posttransplantation with a progressive recovery of pretransplantation status by the second year and in the presence of HSV-1 DNA positivity in bronchoalveolar lavage. As expected, no response was found in seronegative patients. No significant difference in the level of response according to IgM and IgG status was found. Further studies are required to define the role of HSV-1 specific immune response for the clinical-therapeutic management of lung transplant patients and in other clinical settings and to define cut-off levels discriminating between absence/low and strong response to be related to the risk of viral infection/reactivation.
[Mh] Termos MeSH primário: ELISPOT/métodos
Herpes Simples/diagnóstico
Herpesvirus Humano 1/imunologia
Imunidade Celular
Transplante de Pulmão/efeitos adversos
[Mh] Termos MeSH secundário: Adulto
Feminino
Herpes Simples/virologia
Herpesvirus Humano 1/isolamento & purificação
Herpesvirus Humano 1/fisiologia
Seres Humanos
Masculino
Meia-Idade
Linfócitos T/imunologia
Transplantados
Ativação Viral
Adulto Jovem
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180221
[Lr] Data última revisão:
180221
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171130
[St] Status:MEDLINE


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[PMID]:29381918
[Au] Autor:Xu HY; Li CY; Su SS; Yang L; Ye M; Ye JR; Ke PP; Chen CS; Xie YP; Li YP
[Ad] Endereço:Department of Pulmonary and Critical Care Medicine, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, PR China.
[Ti] Título:Diagnosis of tuberculous pleurisy with combination of adenosine deaminase and interferon-γ immunospot assay in a tuberculosis-endemic population: A prospective cohort study.
[So] Source:Medicine (Baltimore);96(47):e8412, 2017 Nov.
[Is] ISSN:1536-5964
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The aim of this study was to identify the optimal cut-off value of T cell enzyme-linked immunospot assay for tuberculosis (T-SPOT.TB) and evaluate its diagnostic performance alone (in the peripheral blood) or in combination with the adenosine deaminase (ADA) activity test (in peripheral blood and the pleural fluid) in patients with tuberculous pleurisy.Adult patients presenting with pleural effusion were included in this prospective cohort study. Tuberculous pleurisy was diagnosed by T-SPOT.TB in peripheral blood and a combination of T-SPOT.TB and ADA activity test in pleural fluid and peripheral blood. Receiver operating characteristic (ROC) curve in combination with multivariate logistic regression was used to evaluate the diagnostic performance of the assays.Among a total of 189 patients with suspected tuberculous pleurisy who were prospectively enrolled in this study, 177 patients were validated for inclusion in the final analysis. ROC analysis revealed that the area under the ROC curve (AUC) for T-SPOT.TB in pleural fluid and peripheral blood was 0.918 and 0.881, respectively, and for the ADA activity test in pleural fluid was 0.944. In addition, 95.5 spot-forming cells (SFCs)/2.5 × 10 cells were determined as the optimal cut-off value for T-SPOT.TB in pleural fluid. Parallel combination of T-SPOT.TB and ADA activity test in pleural fluid showed increased sensitivity (96.9%) and specificity (87.5%), whereas serial combination showed increased specificity (97.5%). The combination of 3 assays had the highest sensitivity at 97.9%, with an AUC value of 0.964.T-SPOT.TB in pleural fluid performed better than that in peripheral blood and the ADA activity test in pleural fluid for tuberculous pleurisy diagnosis. The optimal cut-off value of T-SPOT.TB in pleural fluid was 95.5 SFCs/2.5 × 10 cells. Combination of 3 assays might be a promising approach for tuberculous pleurisy diagnosis.
[Mh] Termos MeSH primário: Adenosina Desaminase/imunologia
ELISPOT/métodos
Interferon gama/imunologia
Tuberculose Pleural/diagnóstico
Tuberculose Pleural/imunologia
[Mh] Termos MeSH secundário: Adulto
Idoso
ELISPOT/normas
Feminino
Testes Hematológicos
Seres Humanos
Masculino
Meia-Idade
Derrame Pleural/imunologia
Estudos Prospectivos
Curva ROC
Valores de Referência
Sensibilidade e Especificidade
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
82115-62-6 (Interferon-gamma); EC 3.5.4.4 (Adenosine Deaminase)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180220
[Lr] Data última revisão:
180220
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:180201
[St] Status:MEDLINE
[do] DOI:10.1097/MD.0000000000008412


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[PMID]:29261651
[Au] Autor:Goedhals D; Paweska JT; Burt FJ
[Ad] Endereço:Division of Virology, National Health Laboratory Service/University of the Free State, Bloemfontein, South Africa.
[Ti] Título:Long-lived CD8+ T cell responses following Crimean-Congo haemorrhagic fever virus infection.
[So] Source:PLoS Negl Trop Dis;11(12):e0006149, 2017 12.
[Is] ISSN:1935-2735
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Crimean-Congo haemorrhagic fever virus (CCHFV) is a member of the Orthonairovirus genus of the Nairoviridae family and is associated with haemorrhagic fever in humans. Although T lymphocyte responses are known to play a role in protection from and clearance of viral infections, specific T cell epitopes have yet to be identified for CCHFV following infection. A panel of overlapping peptides covering the CCHFV nucleoprotein and the structural glycoproteins, GN and GC, were screened by ELISpot assay to detect interferon gamma (IFN-γ) production in vitro by peripheral blood mononuclear cells from eleven survivors with previous laboratory confirmed CCHFV infection. Reactive peptides were located predominantly on the nucleoprotein, with only one survivor reacting to two peptides from the glycoprotein GC. No single epitope was immunodominant, however all but one survivor showed reactivity to at least one T cell epitope. The responses were present at high frequency and detectable several years after the acute infection despite the absence of continued antigenic stimulation. T cell depletion studies confirmed that IFN-γ production as detected using the ELISpot assay was mediated chiefly by CD8+ T cells. This is the first description of CD8+ T cell epitopic regions for CCHFV and provides confirmation of long-lived T cell responses in survivors of CCHFV infection.
[Mh] Termos MeSH primário: Linfócitos T CD8-Positivos/imunologia
Vírus da Febre Hemorrágica da Crimeia-Congo/imunologia
Febre Hemorrágica da Crimeia/imunologia
Imunidade Inata
[Mh] Termos MeSH secundário: Adulto
Idoso
Sequência de Aminoácidos
Estudos de Coortes
ELISPOT
Epitopos/imunologia
Feminino
Glicoproteínas/imunologia
Febre Hemorrágica da Crimeia/virologia
Seres Humanos
Leucócitos Mononucleares/imunologia
Masculino
Meia-Idade
Nucleoproteínas/imunologia
Biblioteca de Peptídeos
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Epitopes); 0 (Glycoproteins); 0 (Nucleoproteins); 0 (Peptide Library)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180212
[Lr] Data última revisão:
180212
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171221
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pntd.0006149


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[PMID]:27774611
[Au] Autor:Tedesco D; Thapa M; Gumber S; Elrod EJ; Rahman K; Ibegbu CC; Magliocca JF; Adams AB; Anania F; Grakoui A
[Ad] Endereço:Emory Vaccine Center, Yerkes National Primate Research Center, Division of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA.
[Ti] Título:CD4 Foxp3 T cells promote aberrant immunoglobulin G production and maintain CD8 T-cell suppression during chronic liver disease.
[So] Source:Hepatology;65(2):661-677, 2017 Feb.
[Is] ISSN:1527-3350
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Persistent hepatotropic viral infections are a common etiologic agent of chronic liver disease. Unresolved infection can be attributed to nonfunctional intrahepatic CD8+ T-cell responses. In light of dampened CD8 T-cell responses, liver disease often manifests systemically as immunoglobulin (Ig)-related syndromes due to aberrant B-cell functions. These two opposing yet coexisting phenomena implicate the potential of altered CD4 T-cell help. Elevated CD4 forkhead box P3-positive (Foxp3+) T cells were evident in both human liver disease and a mouse model of chemically induced liver injury despite marked activation and spontaneous IgG production by intrahepatic B cells. While this population suppressed CD8 T-cell responses, aberrant B-cell activities were maintained due to expression of CD40 ligand on a subset of CD4 Foxp3+ T cells. In vivo blockade of CD40 ligand attenuated B-cell abnormalities in a mouse model of liver injury. A phenotypically similar population of CD4 Foxp3+, CD40 ligand-positive T cells was found in diseased livers explanted from patients with chronic hepatitis C infection. This population was absent in nondiseased liver tissues and peripheral blood. CONCLUSION: Liver disease elicits alterations in the intrahepatic CD4 T-cell compartment that suppress T-cell immunity while concomitantly promoting aberrant IgG mediated manifestations. (Hepatology 2017;65:661-677).
[Mh] Termos MeSH primário: Linfócitos T CD8-Positivos/imunologia
Fatores de Transcrição Forkhead/metabolismo
Imunoglobulina G/imunologia
Cirrose Hepática/imunologia
Cirrose Hepática/patologia
[Mh] Termos MeSH secundário: Análise de Variância
Animais
Células Cultivadas
Doença Crônica
Modelos Animais de Doenças
Ensaio de Imunoadsorção Enzimática
ELISPOT
Citometria de Fluxo
Hepatite C Crônica/imunologia
Hepatite C Crônica/patologia
Hepatócitos
Seres Humanos
Imunoglobulina G/metabolismo
Imuno-Histoquímica
Masculino
Camundongos
Camundongos Endogâmicos C57BL
Distribuição Aleatória
Estatísticas não Paramétricas
Linfócitos T Reguladores/imunologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Forkhead Transcription Factors); 0 (Immunoglobulin G)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:180201
[Lr] Data última revisão:
180201
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161025
[St] Status:MEDLINE
[do] DOI:10.1002/hep.28894


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[PMID]:29261698
[Au] Autor:Nehete PN; Shelton KA; Nehete BP; Chitta S; Williams LE; Schapiro SJ; Abee CR
[Ad] Endereço:Department of Veterinary Sciences, The University of Texas MD Anderson Cancer Center, Bastrop, Texas, United States of America.
[Ti] Título:Effects of transportation, relocation, and acclimation on phenotypes and functional characteristics of peripheral blood lymphocytes in rhesus monkeys (Macaca mulatta).
[So] Source:PLoS One;12(12):e0188694, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Nonhuman primates from domestic sources constitute a small, but critical, proportion of animals studied in research laboratories. Many of these nonhuman primates are raised at one facility and subsequently transported/relocated to another facility for research purposes. We examined the effects of transport, relocation, and acclimation on the phenotype and function of peripheral blood mononuclear cells (PBMCs) in a group of rhesus monkeys that were transported by road for approximately 21 hours from one facility to another. Using a panel of human antibodies and a set of standardized human immune assays, we evaluated the phenotype of lymphocyte subsets by flow, mitogen-specific immune responses of PBMCs in vitro, and levels of circulating cytokines and cortisol in plasma at various time points including immediately before transport, immediately upon arrival, and after approximately 30 days of acclimation. Analyses of blood samples revealed that CD3+ T-cell and CD20+ B-cell populations had decreased significantly immediately after relocation but had recovered within 30 days after arrival at the new facility. Similarly, circulating cortisol and cytokine levels in plasma were significantly higher immediately after relocation; and by the 30-day time point, these differences were no longer significant. However, immune assays of PBMCs indicated that mitogen-specific responses for proliferation, interferon γ (IFN-γ), and perforin were significantly higher after relocation and 30 days of acclimation. These findings have implications on the research participation of transported and relocated nonhuman primates in immunologic research studies, suggesting that 30 days is not sufficient to ensure return to baseline immune homeostasis. These data should be considered when planning research studies in order to minimize potential confounding factors associated with relocation and to maximize study validity.
[Mh] Termos MeSH primário: Aclimatação
Linfócitos/fisiologia
Transportes
[Mh] Termos MeSH secundário: Animais
Biomarcadores/metabolismo
Proliferação Celular/efeitos dos fármacos
Citocinas/sangue
ELISPOT
Feminino
Hidrocortisona/sangue
Interferon gama/metabolismo
Subpopulações de Linfócitos/efeitos dos fármacos
Subpopulações de Linfócitos/fisiologia
Linfócitos/efeitos dos fármacos
Macaca mulatta
Masculino
Mitógenos/farmacologia
Perforina/metabolismo
Fenótipo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Biomarkers); 0 (Cytokines); 0 (Mitogens); 126465-35-8 (Perforin); 82115-62-6 (Interferon-gamma); WI4X0X7BPJ (Hydrocortisone)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180108
[Lr] Data última revisão:
180108
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171221
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0188694


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[PMID]:29045460
[Au] Autor:Razazan A; Behravan J; Arab A; Barati N; Arabi L; Gholizadeh Z; Hatamipour M; Reza Nikpoor A; Momtazi-Borojeni AA; Mosaffa F; Ghahremani MH; Jaafari MR
[Ad] Endereço:Department of Molecular Medicine, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran Iran.
[Ti] Título:Conjugated nanoliposome with the HER2/neu-derived peptide GP2 as an effective vaccine against breast cancer in mice xenograft model.
[So] Source:PLoS One;12(10):e0185099, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:One of the challenging issues in vaccine development is peptide and adjuvant delivery into target cells. In this study, we developed a vaccine and therapeutic delivery system to increase cytotoxic T lymphocyte (CTL) response against a breast cancer model overexpressing HER2/neu. Gp2, a HER2/neu-derived peptide, was conjugated to Maleimide-mPEG2000-DSPE micelles and post inserted into liposomes composed of DMPC, DMPG phospholipids, and fusogenic lipid dioleoylphosphatidylethanolamine (DOPE) containing monophosphoryl lipid A (MPL) adjuvant (DMPC-DMPG-DOPE-MPL-Gp2). BALB/c mice were immunized with different formulations and the immune response was evaluated in vitro and in vivo. ELISpot and intracellular cytokine analysis by flow cytometry showed that the mice vaccinated with Lip-DOPE-MPL-GP2 incited the highest number of IFN-γ+ in CD8+ cells and CTL response. The immunization led to lower tumor sizes and longer survival time compared to the other groups of mice immunized and treated with the Lip-DOPE-MPL-GP2 formulation in both prophylactic and therapeutic experiments. These results showed that co-formulation of DOPE and MPL conjugated with GP2 peptide not only induces high antitumor immunity but also enhances therapeutic efficacy in TUBO mice model. Lip-DOPE-MPL-GP2 formulation could be a promising vaccine and a therapeutic delivery system against HER2 positive cancers and merits further investigation.
[Mh] Termos MeSH primário: Neoplasias da Mama/imunologia
Vacinas Anticâncer/imunologia
Lipossomos/química
Nanopartículas/química
Peptídeos/imunologia
Receptor ErbB-2/metabolismo
Ensaios Antitumorais Modelo de Xenoenxerto
[Mh] Termos MeSH secundário: Sequência de Aminoácidos
Animais
Antígenos de Neoplasias/imunologia
Neoplasias da Mama/patologia
Linhagem Celular Tumoral
Separação Celular
Cromatografia em Camada Delgada
Citocinas/metabolismo
ELISPOT
Feminino
Interferon gama/metabolismo
Interleucina-4/metabolismo
Linfonodos/metabolismo
Maleimidas/química
Camundongos Endogâmicos BALB C
Peptídeos/química
Fenótipo
Fosfatidiletanolaminas/química
Polietilenoglicóis/química
Reação em Cadeia da Polimerase em Tempo Real
Baço/patologia
Linfócitos T Citotóxicos/imunologia
Vacinação
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-methoxy-poly(ethylene glycol 2000)); 0 (Antigens, Neoplasm); 0 (Cancer Vaccines); 0 (Cytokines); 0 (Liposomes); 0 (Maleimides); 0 (Peptides); 0 (Phosphatidylethanolamines); 207137-56-2 (Interleukin-4); 2519R1UGP8 (maleimide); 30IQX730WE (Polyethylene Glycols); 82115-62-6 (Interferon-gamma); EC 2.7.10.1 (ERBB2 protein, human); EC 2.7.10.1 (Receptor, ErbB-2)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171031
[Lr] Data última revisão:
171031
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171019
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0185099


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[PMID]:28953614
[Au] Autor:Barragué H; Condat B; Petitdidier N; Champagne E; Renou C; Izopet J; Abravanel F
[Ad] Endereço:aCentre de Physiopathologie de Toulouse Purpan, INSERM U1043/CNRS UMR5282/Université Toulouse III Paul-Sabatier, Toulouse bHôpital Sainte Camille, Bry sur Marne cDivision of Hepatology, Centre Hospitalier de Hyères, Hyères dCentre Hospitalier Universitaire de Toulouse, Hôpital Purpan, Laboratoire de virologie, Centre National de Référence Hépatite E, Institut fédératif de biologie de Purpan, Toulouse, France.
[Ti] Título:Chronic hepatitis E virus infection in a cirrhotic patient: A case report.
[So] Source:Medicine (Baltimore);96(39):e7915, 2017 Sep.
[Is] ISSN:1536-5964
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:RATIONALE: Acute hepatitis E virus (HEV) infections are usually self-limiting in immunocompetent patients. HEV persistence has been described only in immunosuppressed patients such as solid-organ transplant recipients, patients with hematological diseases, or patients with human immunodeficiency virus (HIV) infection. PATIENT CONCERNS: A 61-year-old patient was admitted in hospital for jaundice and asthenia. DIAGNOSES: The patient had underlying cirrhosis and developed a chronic HEV infection. INTERVENTION: Ribavirin therapy was initiated. OUTCOMES: Ribavirin therapy for 12 months allowed the clearance of the virus and HEV viral load remained undetectable thereafter. This patient had taken no immunosuppressive drugs, was not suffering from any autoimmune disease and was not infected with HIV. We studied the patient's anti-HEV immune response months after the viral clearance. His peripheral blood mononuclear cells (PBMC) were stimulated in vitro by HEV peptides. The patient had a mild T lymphopenia, but polyclonal stimulation of PBMC showed a robust T cell response. The response of his anti-HEV specific interferon-γ producing T cells was low. LESSONS: Other studies are now needed to identify the population with a chronic evolution of HEV infection despite no apparent immunodepression.
[Mh] Termos MeSH primário: Antivirais/uso terapêutico
Hepatite E/complicações
Hepatite E/tratamento farmacológico
Cirrose Hepática/complicações
Ribavirina/uso terapêutico
[Mh] Termos MeSH secundário: ELISPOT
Hepatite E/imunologia
Hepatite Crônica/complicações
Hepatite Crônica/tratamento farmacológico
Hepatite Crônica/imunologia
Seres Humanos
Interferon gama/sangue
Cirrose Hepática/imunologia
Cirrose Hepática/virologia
Masculino
Meia-Idade
[Pt] Tipo de publicação:CASE REPORTS; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antiviral Agents); 49717AWG6K (Ribavirin); 82115-62-6 (Interferon-gamma)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171013
[Lr] Data última revisão:
171013
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:170928
[St] Status:MEDLINE
[do] DOI:10.1097/MD.0000000000007915


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[PMID]:28931091
[Au] Autor:Thomas AS; Jones KL; Gandhi RT; McMahon DK; Cyktor JC; Chan D; Huang SH; Truong R; Bosque A; Macedo AB; Kovacs C; Benko E; Eron JJ; Bosch RJ; Lalama CM; Simmens S; Walker BD; Mellors JW; Jones RB
[Ad] Endereço:Department of Microbiology Immunology and Tropical Medicine, George Washington University, Washington, District of Columbia, United States of America.
[Ti] Título:T-cell responses targeting HIV Nef uniquely correlate with infected cell frequencies after long-term antiretroviral therapy.
[So] Source:PLoS Pathog;13(9):e1006629, 2017 Sep.
[Is] ISSN:1553-7374
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:HIV-specific CD8+ T-cell responses limit viral replication in untreated infection. After the initiation of antiretroviral therapy (ART), these responses decay and the infected cell population that remains is commonly considered to be invisible to T-cells. We hypothesized that HIV antigen recognition may persist in ART-treated individuals due to low-level or episodic protein expression. We posited that if persistent recognition were occurring it would be preferentially directed against the early HIV gene products Nef, Tat, and Rev as compared to late gene products, such as Gag, Pol, and Env, which have higher barriers to expression. Using a primary cell model of latency, we observed that a Nef-specific CD8+ T-cell clone exhibited low-level recognition of infected cells prior to reactivation and robust recognition shortly thereafter. A Gag-specific CD8+ T-cell clone failed to recognized infected cells under these conditions, corresponding with a lack of detectable Gag expression. We measured HIV-specific T-cell responses in 96 individuals who had been suppressed on ART for a median of 7 years, and observed a significant, direct correlation between cell-associated HIV DNA levels and magnitudes of IFN-γ-producing Nef/Tat/Rev-specific T-cell responses. This correlation was confirmed in an independent cohort (n = 18). Correlations were not detected between measures of HIV persistence and T-cell responses to other HIV antigens. The correlation with Nef/Tat/Rev-specific T-cells was attributable to Nef-specific responses, the breadth of which also correlated with HIV DNA levels. These results suggest that ongoing Nef expression in ART-treated individuals drives preferential maintenance and/or expansion of T-cells reactive to this protein, implying sensing of infected cells by the immune system. The direct correlation, however, suggests that recognition does not result in efficient elimination of infected cells. These results raise the possibility that enhancing the cytolytic activity of Nef-specific T-cells may lead to reductions in infected cell frequencies, even in the absence of therapeutic latency reversal.
[Mh] Termos MeSH primário: Linfócitos T CD8-Positivos/imunologia
Infecções por HIV/imunologia
Latência Viral/imunologia
Produtos do Gene nef do Vírus da Imunodeficiência Humana/imunologia
[Mh] Termos MeSH secundário: Antirretrovirais/uso terapêutico
ELISPOT
Infecções por HIV/tratamento farmacológico
Seres Humanos
Reação em Cadeia da Polimerase
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anti-Retroviral Agents); 0 (nef Gene Products, Human Immunodeficiency Virus)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171018
[Lr] Data última revisão:
171018
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170921
[St] Status:MEDLINE
[do] DOI:10.1371/journal.ppat.1006629


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[PMID]:28892515
[Au] Autor:Sumonwiriya M; Paris DH; Sunyakumthorn P; Anantatat T; Jenjaroen K; Chumseng S; Im-Erbsin R; Tanganuchitcharnchai A; Jintaworn S; Blacksell SD; Chowdhury FR; Kronsteiner B; Teparrukkul P; Burke RL; Lombardini ED; Richards AL; Mason CJ; Jones JW; Day NPJ; Dunachie SJ
[Ad] Endereço:Mahidol Oxford Tropical Medicine Research Unit, Mahidol University, Bangkok, Thailand.
[Ti] Título:Strong interferon-gamma mediated cellular immunity to scrub typhus demonstrated using a novel whole cell antigen ELISpot assay in rhesus macaques and humans.
[So] Source:PLoS Negl Trop Dis;11(9):e0005846, 2017 Sep.
[Is] ISSN:1935-2735
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Scrub typhus is a febrile infection caused by the obligate intracellular bacterium Orientia tsutsugamushi, which causes significant morbidity and mortality across the Asia-Pacific region. The control of this vector-borne disease is challenging due to humans being dead-end hosts, vertical maintenance of the pathogen in the vector itself, and a potentially large rodent reservoir of unclear significance, coupled with a lack of accurate diagnostic tests. Development of an effective vaccine is highly desirable. This however requires better characterization of the natural immune response of this neglected but important disease. Here we implement a novel IFN-γ ELISpot assay as a tool for studying O. tsutsugamushi induced cellular immune responses in an experimental scrub typhus rhesus macaque model and human populations. Whole cell antigen for O. tsutsugamushi (OT-WCA) was prepared by heat inactivation of Karp-strain bacteria. Rhesus macaques were infected intradermally with O. tsutsugamushi. Freshly isolated peripheral blood mononuclear cells (PBMC) from infected (n = 10) and uninfected animals (n = 5) were stimulated with OT-WCA, and IFN-γ secreting cells quantitated by ELISpot assay at five time points over 28 days. PBMC were then assayed from people in a scrub typhus-endemic region of Thailand (n = 105) and responses compared to those from a partially exposed population in a non-endemic region (n = 14), and to a naïve population in UK (n = 12). Mean results at Day 0 prior to O. tsutsugamushi infection were 12 (95% CI 0-25) and 15 (2-27) spot-forming cells (SFC)/106 PBMC for infected and control macaques respectively. Strong O. tsutsugamushi-specific IFN-γ responses were seen post infection, with ELISpot responses 20-fold higher than baseline at Day 7 (mean 235, 95% CI 200-270 SFC/106 PBMC), 105-fold higher at Day 14 (mean 1261, 95% CI 1,097-1,425 SFC/106 PBMC), 125-fold higher at Day 21 (mean 1,498, 95% CI 1,496-1,500 SFC/106 PBMC) and 118-fold higher at Day 28 (mean 1,416, 95% CI 1,306-1,527 SFC/106 PBMC). No significant change was found in the control group at any time point compared to baseline. Humans from a scrub typhus endemic region of Thailand had mean responses of 189 (95% CI 88-290) SFC/106 PBMC compared to mean responses of 40 (95% CI 9-71) SFC/106 PBMC in people from a non-endemic region and 3 (95% CI 0-7) SFC/106 PBMC in naïve controls. In summary, this highly sensitive assay will enable field immunogenicity studies and further characterization of the host response to O. tsutsugamushi, and provides a link between human and animal models to accelerate vaccine development.
[Mh] Termos MeSH primário: Antígenos de Bactérias/imunologia
ELISPOT/métodos
Imunidade Celular
Interferon gama/imunologia
Leucócitos Mononucleares/imunologia
Orientia tsutsugamushi/imunologia
Tifo por Ácaros/imunologia
[Mh] Termos MeSH secundário: Animais
Seres Humanos
Interferon gama/biossíntese
Cinética
Macaca mulatta
Modelos Animais
Orientia tsutsugamushi/isolamento & purificação
Tifo por Ácaros/diagnóstico
Tailândia/epidemiologia
Tifo Endêmico Transmitido por Pulgas
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antigens, Bacterial); 82115-62-6 (Interferon-gamma)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171017
[Lr] Data última revisão:
171017
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170912
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pntd.0005846


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[PMID]:28859168
[Au] Autor:Salles ÉM; Menezes MN; Siqueira R; Borges da Silva H; Amaral EP; Castillo-Méndez SI; Cunha I; Cassado ADA; Vieira FS; Olivieri DN; Tadokoro CE; Alvarez JM; Coutinho-Silva R; D'Império-Lima MR
[Ad] Endereço:Departamento de Imunologia, Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo, Brazil.
[Ti] Título:P2X7 receptor drives Th1 cell differentiation and controls the follicular helper T cell population to protect against Plasmodium chabaudi malaria.
[So] Source:PLoS Pathog;13(8):e1006595, 2017 Aug.
[Is] ISSN:1553-7374
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:A complete understanding of the mechanisms underlying the acquisition of protective immunity is crucial to improve vaccine strategies to eradicate malaria. However, it is still unclear whether recognition of damage signals influences the immune response to Plasmodium infection. Adenosine triphosphate (ATP) accumulates in infected erythrocytes and is released into the extracellular milieu through ion channels in the erythrocyte membrane or upon erythrocyte rupture. The P2X7 receptor senses extracellular ATP and induces CD4 T cell activation and death. Here we show that P2X7 receptor promotes T helper 1 (Th1) cell differentiation to the detriment of follicular T helper (Tfh) cells during blood-stage Plasmodium chabaudi malaria. The P2X7 receptor was activated in CD4 T cells following the rupture of infected erythrocytes and these cells became highly responsive to ATP during acute infection. Moreover, mice lacking the P2X7 receptor had increased susceptibility to infection, which correlated with impaired Th1 cell differentiation. Accordingly, IL-2 and IFNγ secretion, as well as T-bet expression, critically depended on P2X7 signaling in CD4 T cells. Additionally, P2X7 receptor controlled the splenic Tfh cell population in infected mice by promoting apoptotic-like cell death. Finally, the P2X7 receptor was required to generate a balanced Th1/Tfh cell population with an improved ability to transfer parasite protection to CD4-deficient mice. This study provides a new insight into malaria immunology by showing the importance of P2X7 receptor in controlling the fine-tuning between Th1 and Tfh cell differentiation during P. chabaudi infection and thus in disease outcome.
[Mh] Termos MeSH primário: Diferenciação Celular/imunologia
Ativação Linfocitária/imunologia
Malária/imunologia
Receptores Purinérgicos P2X7/imunologia
Linfócitos T Auxiliares-Indutores/imunologia
Células Th1/imunologia
[Mh] Termos MeSH secundário: Transferência Adotiva
Animais
Modelos Animais de Doenças
Ensaio de Imunoadsorção Enzimática
ELISPOT
Eritrócitos/parasitologia
Feminino
Imunofluorescência
Marcação In Situ das Extremidades Cortadas
Masculino
Camundongos
Camundongos Endogâmicos C57BL
Camundongos Knockout
Plasmodium chabaudi/imunologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Receptors, Purinergic P2X7)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171003
[Lr] Data última revisão:
171003
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170901
[St] Status:MEDLINE
[do] DOI:10.1371/journal.ppat.1006595



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