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1.
J Viral Hepat ; 24(11): 917-926, 2017 11.
Artigo em Inglês | MEDLINE | ID: mdl-28414896

RESUMO

Natural killer (NK) cells have long been thought of as a purely innate immune cell population, but increasing reports have described developmental and functional qualities of NK cells that are commonly associated with cells of the adaptive immune system. Of these features, the ability of NK cells to acquire functional qualities associated with immunological memory and continuous differentiation resulting in the formation of specific NK cell repertoires has recently been highlighted in viral infection settings. By making use of a unique cohort of monitored, at-risk intravenous drug users in this study, we were able to dissect the phenotypic and functional parameters associated with NK cell differentiation and NK cell memory in patients 3 years after acute HCV infection and either the subsequent self-clearance or progression to chronicity. We observed increased expression of cytolytic mediators and markers CD56bright and NKp46+ of NK cells in patients with chronic, but not self-limited HCV infection. Patients with a self-limited infection expressed higher levels of differentiation-associated markers CD57 and KIRs, and lower levels of NKG2A. A more extensively differentiated NK cell phenotype is associated with self-clearance in HCV patients, while the NK cells of chronic patients exhibited more naïve and effector NK cell phenotypic and functional characteristics. The identification of these distinct NK cell repertoires may shed light on the role NK cells play in determining the outcome of acute HCV infections, and the underlying immunological defects that lead to chronicity.


Assuntos
Diferenciação Celular , Hepacivirus/imunologia , Hepatite C/imunologia , Hepatite C/virologia , Memória Imunológica , Células Matadoras Naturais/citologia , Células Matadoras Naturais/imunologia , Adulto , Biomarcadores , Antígeno CD56/metabolismo , Diferenciação Celular/imunologia , Estudos de Coortes , Citocinas/metabolismo , Feminino , Genótipo , Granzimas/metabolismo , Hepatite C/metabolismo , Humanos , Imunofenotipagem , Células Matadoras Naturais/metabolismo , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Receptores Desencadeadores da Citotoxicidade Natural/metabolismo , Ligante Indutor de Apoptose Relacionado a TNF/metabolismo , Carga Viral , Adulto Jovem
2.
Clin Exp Immunol ; 173(2): 259-67, 2013 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-23607448

RESUMO

Intravenous immunoglobulin (IVIg) is used to treat autoimmune and systemic inflammatory diseases caused by derailment of humoral and cellular immunity. In this study we investigated whether IVIg treatment can modulate regulatory T cells (Tregs ) in humans in vivo. Blood was collected from IVIg-treated patients with immunodeficiency or autoimmune disease who were treated with low-dose (n = 12) or high-dose (n = 15) IVIg before, immediately after and at 7 days after treatment. Percentages and activation status of circulating CD4(+) CD25(+) forkhead box protein 3 (FoxP3(+)) Tregs and of conventional CD4(+) FoxP3(-) T-helper cells (Tconv) were measured. The suppressive capacity of Tregs purified from blood collected at the time-points indicated was determined in an ex-vivo assay. High-dose, but not low-dose, IVIg treatment enhanced the activation status of circulating Tregs , as shown by increased FoxP3 and human leucocyte antigen D-related (HLA-DR) expression, while numbers of circulating Tregs remained unchanged. The enhanced activation was sustained for at least 7 days after infusion, and the suppressive capacity of purified Tregs was increased from 41 to 70% at day 7 after IVIg treatment. The activation status of Tconv was not affected by IVIg. We conclude that high-dose IVIg treatment activates Tregs selectively and enhances their suppressive function in humans in vivo. This effect may be one of the mechanisms by which IVIg restores imbalanced immune homeostasis in patients with autoimmune and systemic inflammatory disorders.


Assuntos
Doenças Autoimunes/tratamento farmacológico , Imunoglobulinas Intravenosas/administração & dosagem , Síndromes de Imunodeficiência/tratamento farmacológico , Linfócitos T Auxiliares-Indutores/efeitos dos fármacos , Linfócitos T Reguladores/efeitos dos fármacos , Adulto , Idoso , Doenças Autoimunes/imunologia , Antígenos CD4/metabolismo , Protocolos Clínicos , Cálculos da Dosagem de Medicamento , Feminino , Fatores de Transcrição Forkhead/metabolismo , Antígenos HLA-DR/genética , Antígenos HLA-DR/metabolismo , Humanos , Síndromes de Imunodeficiência/imunologia , Terapia de Imunossupressão , Subunidade alfa de Receptor de Interleucina-2/metabolismo , Ativação Linfocitária/efeitos dos fármacos , Masculino , Pessoa de Meia-Idade , Linfócitos T Auxiliares-Indutores/imunologia , Linfócitos T Reguladores/imunologia , Adulto Jovem
3.
J Clin Microbiol ; 46(10): 3215-21, 2008 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-18685007

RESUMO

Using a case control approach, we performed a two-way comparison study between GP5+/6+-PCR and HPV SPF(10)-Line Blot 25 (SPF(10)) assays for detection of 14 types of high-risk human papillomavirus (hrHPV) in samples from women with normal cytology results who had or developed grade 3 cervical intraepithelial neoplasia (CIN 3). Samples were pooled from two cohorts, i.e., women participating in population-based screening and women attending a gynecological outpatient clinic. Cases (n = 45) were women with histologically confirmed CIN 3 diagnosed within a median follow-up time of 2.7 (range, 0.2 to 7.9) years. Control samples were from women (n = 264) who had developed CIN 1 lesions at maximum (median follow-up at 5.8 [range, 0 to 10] years). Identical numbers of cases tested positive for 1 or more of the 14 hrHPV types by both systems (40/45; McNemar; P = 1.0). Conversely, SPF(10) scored significantly more controls as hrHPV positive than did GP5+/6+-PCR (95/264 versus 29/264; McNemar; P < 0.001). Consequently, women with normal cytology results and an hrHPV GP5+/6+-PCR-positive test exhibited a risk of CIN 3 that was 4.5 times higher (odds ratio [OR], 65; 95% confidence interval [95%CI], 24 to 178) than that seen for women with an hrHPV-positive SPF(10) test (OR, 14; 95%CI, 5 to 38)). Similar results were obtained after analysis of both cohorts separately. Discrepancy analysis by viral load assessment for the most common discordant hrHPV types (HPV16, -18, and -52) showed that samples which were SPF(10) positive only for these types had viral loads significantly lower than those for samples that were positive by both assays (analysis of variance; P < or = 0.006). Our data indicate that GP5+/6+-PCR has a better clinical performance than SPF(10) for women who are diagnosed with CIN 3 after prior normal cytology results. The extra positivity scored by SPF(10) mainly involved infections characterized by low viral loads that do not result in CIN 3.


Assuntos
Hibridização de Ácido Nucleico/métodos , Papillomaviridae/isolamento & purificação , Infecções por Papillomavirus/diagnóstico , Reação em Cadeia da Polimerase/métodos , Displasia do Colo do Útero/virologia , Útero/virologia , Adulto , Estudos de Casos e Controles , Feminino , Humanos , Pessoa de Meia-Idade , Papillomaviridae/genética , Infecções por Papillomavirus/virologia , Valor Preditivo dos Testes , Sensibilidade e Especificidade , Proteínas Virais/genética
4.
J Clin Microbiol ; 43(9): 4868-71, 2005 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-16145162

RESUMO

We compared real-time LightCycler and TaqMan assays and the GP5+/6+ PCR/enzyme immunoassay (EIA) to assess the human papillomavirus type 16 (HPV16) load in cervical scrape specimens. Both real-time PCR assays determined the HPV16 load in scrape specimens similarly. The level of agreement between these assays and the GP5+/6+ PCR/EIA was low (P = 0.004), suggesting that the latter method is not suited for quantifying HPV16 DNA.


Assuntos
Colo do Útero/virologia , DNA Viral/análise , Papillomaviridae/isolamento & purificação , Infecções por Papillomavirus/diagnóstico , Reação em Cadeia da Polimerase/métodos , Sondas de DNA de HPV , Feminino , Humanos , Técnicas Imunoenzimáticas , Papillomaviridae/genética , Infecções por Papillomavirus/virologia , Taq Polimerase , Esfregaço Vaginal
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