Increased number and function of natural killer cells in human immunodeficiency virus 1-positive subjects co-infected with herpes simplex virus 2

P>Natural killer (NK) cells bridge the interface between innate and adaptive immunity and are implicated in the control of herpes simplex virus 2 (HSV-2) infection. In subjects infected with human immunodeficiency virus 1 (HIV-1), the critical impact of the innate immune response on disease progression has recently come into focus. Higher numbers of NK cells are associated with lower HIV-1 plasma viraemia. Individuals with the compound genotype of killer cell immunoglobulin-like receptor (KIR) 3DS1 and human leucocyte antigen (HLA)-Bw4-80I, or who have alleles of KIR3DL1 that encode proteins highly expressed on the NK cell surface, have a significant delay in disease progression. We studied the effect of HSV-2 co-infection in HIV-1-infected subjects, and show that HSV-2 co-infection results in a pan-lymphocytosis, with elevated absolute numbers of CD4+ and CD8+ T cells, and NK cells. The NK cells in HSV-2 co-infected subjects functioned more efficiently, with an increase in degranulation after in vitro stimulation. The number of NK cells expressing the activating receptors NKp30 and NKp46, and expressing KIR3DL1 or KIR3DS1, was inversely correlated with HIV-1 plasma viral load in subjects mono-infected with HIV-1, but not in subjects co-infected with HSV-2. This suggests that HSV-2 infection mediates changes within the NK cell population that may affect immunity in HIV-1 infection.

Lower numbers of circulating natural killer T (NK T) cells in individuals with human T lymphotropic virus type 1 (HTLV-1) associated neurological disease

Human T lymphotropic virus type 1 (HTLV-1) infects 10-20 million people worldwide. The majority of infected individuals are asymptomatic; however, approximately 3% develop the debilitating neurological disease HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). There is also currently no cure, vaccine or effective therapy for HTLV-1 infection, and the mechanisms for progression to HAM/TSP remain unclear. NK T cells are an immunoregulatory T cell subset whose frequencies and effector functions are associated critically with immunity against infectious diseases. We hypothesized that NK T cells are associated with HAM/TSP progression. We measured NK T cell frequencies and absolute numbers in individuals with HAM/TSP infection from two cohorts on two continents: Sao Paulo, Brazil and San Francisco, CA, USA, and found significantly lower levels when compared with healthy subjects and/or asymptomatic carriers. Also, the circulating NK T cell compartment in HAM/TSP subjects is comprised of significantly more CD4(+) and fewer CD8(+) cells than healthy controls. These findings suggest that lower numbers of circulating NK T cells and enrichment of the CD4(+) NK T subset are associated with HTLV-1 disease progression.

Lower cytokine secretion ex vivo by natural killer T cells in HIV-infected individuals is associated with higher CD161 expression

Objective: Natural killer T (NKT) cells are efficiently targeted by HIV and severely reduced in numbers in the circulation of infected individuals. The functional capacity of the remaining NKT cells in HIV-infected individuals is poorly characterized. This study measured NKT cell cytokine production directly ex vivo and compared these responses with both the disease status and NKT subset distribution of individual patients. Methods: NKT cell frequencies, subsets, and ex-vivo effector functions were measured in the peripheral blood mononuclear cells of HIV-infected patients and healthy controls by flow cytometry. We measured cytokines from NKT cells after stimulation with either a-galactosyl ceramide-loaded CD1d dimers (DimerX-alpha GalCer) or phorbol myristate acetate and ionomycin. Results: The frequencies of NKT cells secreting interferon-gamma and tumor necrosis factor-alpha were significantly lower in HIV-infected patients than healthy controls after DimerX-alpha GalCer treatment, but responses were similar after treatment with phorbol myristate acetate and ionomycin. The magnitude of the interferon-gamma response to DimerX-alpha GalCer correlated inversely with the number of years of infection. Both interferon-gamma and tumor necrosis factor-alpha production in response to DimerX-alpha GalCer correlated inversely with CD161 expression. Conclusion: The ex-vivo Th1 responses of circulating NKT cells to CD1d-glycolipid complexes are impaired in HIV-infected patients. NKT cell functions may be progressively lost over time in HIV infection, and CD161 is implicated in the regulation of NKT cell responsiveness. (C) 2009 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins

Angiogenic non-Hodgkin T/natural killer (NK)-cell lymphoma: Report of three cases

Angiogenic T/natural killer (NK)-cell lymphoma is a non-Hodgkin lymphoma characterized by necrosis and vascular destruction that is strongly associated with Epstein-Barr virus and AIDS. Early diagnosis is essential to improve the chances of patient survival, but severe local inflammatory infiltrate impairs histologic diagnosis by obscuring neoplastic cells. The most common markers are CD2, CD56, cytoplasmic CD3, and CD43 EBV We describe 3 cases of angiogenic T/NK-cell lymphoma that show the diverse Presentation of the same disease. Patient I was HIV positive and had nasal obstruction, facial edema, and ulceration of the nasal mucosa. Patient 2 had fever, a sore throat, and weight loss. Patient 3 had facial edema, fever, proptosis, and rapid development Of neurologic alterations. Several biopsies were needed for histologic confirmation in these patients, despite positivity for the CD3 and CD56 markers.

Dendritic cells rapidly undergo apoptosis in vitro following culture with activated CD4(+) V alpha 24 natural killer T cells expressing CD40L

Human V alpha 24 natural killer T (V alpha 24NKT) cells are activated by -glycosylceramide-pulsed dendritic cells (DCs) in a CDld-dependent and T-cell receptor-mediated manner. There are two major subpopulations of V alpha 24NKT cells, CD4(-) CD8(-) V alpha 24NKT and CD4(+) V alpha 24NKT cells. We have recently shown that activated CD4(-) CD8 V alpha 24NKT cells have cytotoxic activity against DCs, but knowledge of the molecules responsible for cytotoxicity of V alpha 24NKT cells is currently limited. We aimed to investigate whether CD4(+) V alpha 24NKT cells also have cytotoxic activity against DCs and to determine the mechanisms underlying any observed cytotoxic activity. We demonstrated that activated CD4(+) V alpha 24NKT cells [CD40 ligand (CD40L) -positive] have cytotoxic activity against DCs (strongly CD40-positive), but not against monocytes (weakly CD40-positive) or phytohaemagglutinin blast T cells (CD40-negative), and that apoptosis of DCs significantly contributes to the observed cytotoxicity. The apoptosis of DCs following culture with activated CD4(+) V alpha 24NKT cells, but not with resting CD4(+) V alpha 24NKT cells (CD40L-negative), was partially inhibited by anti-CD40L mAb, Direct ligation of CD40 on the DCs by the anti-CD40 antibody also induced apoptosis of DCs. Our results suggest that CD40-CD40L interaction plays an important role in the induction of apoptosis of DCs following culture with activated CD4+ Va24NKT cells. The apoptosis of DCs from normal donors. triggered by the CD40-CD40L interaction, may contribute to the homeostatic regulation of the normal human immune system, preventing the interminable activation of activated CD4(+) V alpha 24NKT cells by virtue of apoptosis of DCs.

The relationship of natural killer cell counts, perforin mRNA and CD2 expression to post-exercise natural killer cell activity in humans

The aim of this study was to further investigate the mechanism of suppression of natural killer (NK) cell cytotoxic activity In peripheral blood following strenuous exercise. Blood was collected for analysis of NK cell concentration, cytotoxic activity, CD2 surface expression and perforin gene expression from runners (RUN, n = 6) and resting controls (CONTROL, n = 4) pre-exercise, 0, 1.5, 5, and 24 h following a 60-min treadmill run at 80% of VO2 peak. Natural killer cytotoxic activity, measured using a whole blood chromium release assay, fluctuated minimally in the CONTROL group and increased by 63% and decreased by 43% 0 and 1.5 h post-exercise, respectively, in the RUN group (group x time, P < 0.001). Lytic index (cytotoxic activity per cell) did not change. Perforin mRNA, measured using quantitative real-time polymerase chain reaction (ORT-PCR) decreased from pre- to post-exercise and remained decreased through 24 h, The decrease from pre- to 0 In post-exercise was seen predominately in the RUN group and was inversely correlated r = - 0.95) to pre-exercise perform mRNA. The NK cell surface expression of CD2 (lymphocyte function-associated antigen-2) was determined using fluorescent antibodies and flow cytometry, There was no change in the proportion of NK cells expressing CD2 or CD2 density, We conclude that (1) numerical redistribution accounted for most of the change in NK cytotoxic activity following a strenuous run, (2) decrease in perforin gene expression during the run was inversely related to pre-exercise levels but did not parallel changes in cytotoxic activity, and (3) CD2 surface expression was not affected by exercise.

Inhibition of early tumor growth requires Jα18-positive (natural killer T) cells

The role of natural killer T (NKT) cells in the immune response to tumor cells has been largely unexplored. As a model of adoptive tumor immunotherapy, cells from the draining lymph nodes of mice immunized with a tumor-specific or irrelevant antigen were transferred to naive recipients with established tumor. Inhibition of early tumor growth (day 4) required the transfer of both CD8(+) and Jalpha18(+) (NKT) cells from immunized animals without regard to immunogen. In contrast, CD8(+) cells, but not Jalpha18(+) cells, were necessary for the inhibition of late tumor growth (day 8). Thus, the developing tumor changes in sensitivity to NKT-mediated events and the role for NKT cells cannot be replaced by the presence of tumor-specific cells during early tumor growth. This suggests that recruitment/activation of Jalpha18(+) NKT cells is an important consideration during the immune therapy of early stage tumors.

Sistema de Gest??o de Conv??nios e Contratos de Repasse (Siconv). Um novo paradigma nas transfer??ncias volunt??rias da Uni??o

O Sistema de Gest??o de Conv??nios e Contratos de Repasse (Siconv) ?? a iniciativa do Governo Federal respons??vel por todo o ciclo de vida dos conv??nios, contratos de repasse e termos de parceria, no qual s??o registrados os atos, desde a formaliza????o da proposta at?? a presta????o de contas final. O Siconv inova no modelo de gest??o, proporciona celeridade aos procedimentos e desburocratiza as atividades fins, com foco na substitui????o do processo f??sico pelo eletr??nico e no registro de todos os procedimentos, o que permite maior transpar??ncia na execu????o das transfer??ncias volunt??rias da Uni??o. Destaca- se ainda que a disponibiliza????o do sistema aos usu??rios e tamb??m para a sociedade por meio do endere??o eletr??nico www.convenios.gov.br deve ser considerada como grande fator de inova????o, uma vez que, mesmo indiretamente, se apresenta como mais uma ferramenta de controle social.

Sistema de registro eletr??nico de ponto

O Sistema de Registro Eletr??nico de Ponto (SREP) representou um importante avan??o nos instrumentos de prote????o e seguran??a dos trabalhadores e empresas que utilizam o ponto eletr??nico, por coibir fraudes de altera????o dos hor??rios efetivamente registrados, de supress??o ou de impedimento na marca????o de horas extras. Ap??s investiga????o das modalidades de fraudes e dos sistemas que propiciavam as adultera????es, a equipe t??cnica do Minist??rio do Trabalho e Emprego (MTE) desenvolveu o modelo de regulamenta????o, consolidado na Portaria n?? 1.510/2009, que garante as marca????es dos hor??rios de jornada de trabalho sem possibilidade de adultera????o. O SREP ?? composto de um hardware e um software. O hardware, Registrador Eletr??nico de Ponto (REP), preserva as marca????es de ponto e fornece ao trabalhador o seu comprovante. O software opera nos computadores das empresas, permitindo o tratamento seguro dos dados para pagamento das horas trabalhadas. S?? em 2010, o SREP recuperou uma sonega????o de R$ 1,5 bilh??o em sal??rios e R$ 446,6 milh??es em contribui????es previdenci??rias e Fundo de Garantia do Tempo de Servi??o (FGTS)

Spade-PRO: Sistema de Prospec????o e An??lise de Desvios em Exames: provas objetivas

Sistema desenvolvido e aplicado durante a Opera????o Tormenta para identificar suspeitos de fraudar as provas objetivas de concursos p??blicos. O Sistema de Prospec????o e An??lise de Desvios em Exames (Spade-PRO) serviu de base para auditar os concursos p??blicos realizados pela Pol??cia Federal nos anos de 2001, 2004 e 2009. Em raz??o da efetividade do sistema, a sua utiliza????o foi estendida para os concursos p??blicos realizados pelas seguintes institui????es: Ag??ncia Nacional de Avia????o Civil (Anac), Ag??ncia Brasileira de Intelig??ncia (Abin), Tribunal de Justi??a do Estado de S??o Paulo (TJSP) e para o Exame da Ordem dos Advogados do Brasil (OAB). Os dados obtidos, utilizados nas a????es criminais que apuraram a responsabilidade pelas fraudes, foram fundamentais para evitar o ingresso ilegal de pessoas no servi??o p??blico. O sistema ser?? utilizado pela Pol??cia Federal para auditar os pr??ximos concursos do ??rg??o e est?? dispon??vel para ser aplicado por qualquer institui????o que solicite a realiza????o da auditoria em seus processos seletivos

Sistema de coleta on-line do Censo Escolar da Educa????o B??sica (Educacenso)

O Educacenso ?? um sistema eletr??nico de coleta de informa????es educacionais composto por um aplicativo web, que permite a coleta, migra????o e altera????o de dados educacionais das escolas em todo o territ??rio nacional, e por um banco de dados relacional, que armazena de forma sistem??tica todas estas informa????es. O Educacenso representa uma inova????o, pois se trata de um banco de dados ??nico, de base nacional, alimentado por dados e informa????es que v??m diretamente das escolas, por meio da internet. Constitui-se no mais completo cadastro de escolas, alunos e docentes do pa??s. A constru????o de um banco de dados com informa????es individualizadas amplia as possibilidades de comunica????o com outras bases de dados do governo federal. O novo desenho metodol??gico e a utiliza????o de recursos de tecnologia da informa????o permitiram ampliar a precis??o e a fidedignidade dos dados do Censo Escolar, o que possibilita realiza????o de ajustes na pol??tica educacional e maior efetividade do gasto p??blico com a educa????o b??sica

Sistema de Controle log??stico de Medicamentos Antirretrovirais (SICLOM)

O Sistema de Controle Log??stico de Medicamentos Antirretrovirais (Siclom) ?? uma ferramenta criada com o objetivo de gerenciamento log??stico dos medicamentos antirretrovirais (ARV) e de aprimoramento da qualifica????o da dispensa????o. Esse sistema permite que o departamento de DST, Aids e Hepatites Virais, secretarias estaduais e municipais de Sa??de mantenham-se atualizados em rela????o ao fornecimento, dispensa????o de medicamentos aos pacientes em tratamento conforme as recomenda????es existentes no Consenso Terap??utico Brasileiro, al??m do controle dos estoques de cada medicamento nas v??rias regi??es do pa??s. As informa????es de consumo e estoques s??o fundamentais para que o adequado suprimento aos estados ocorra evitando, assim, a ruptura dos estoques locais e preju??zo no atendimento aos pacientes. Atualmente utilizam o sistema 670 unidades dispensadoras de medicamentos, distribu??das em todo o Brasil; 27 coordena????es estaduais de DST/Aids; 61 almoxarifados; e 936 maternidades

Sistema Nacional de Informa????es de Defesa do Consumidor (Sindec)

O Sistema Nacional de Informa????es de Defesa do Consumidor integra Procons de 23 estados brasileiros e do Distrito Federal. ?? um sistema que permite o registro de demandas individuais de consumidores, bem como a gest??o dos procedimentos que tratam essas demandas. O Sindec consolida os registros em bases locais e forma um banco nacional de informa????es sobre problemas enfrentados por consumidores. Essas informa????es podem ser consultadas por consumidores, pelos Procons integrados e por toda a sociedade, por meio do s??tio www.mj.gov.br/sindec. O Sindec re??ne informa????es de mais de 80 Procons (entre estaduais, municipais e do Distrito Federal), est?? presente em mais de 110 cidades de todas as regi??es brasileiras e consolida registros de demandas de mais de 2 milh??es de consumidores contra mais de 10 mil fornecedores

Sistema de Avalia????o de Desempenho Individual do Inmetro (Siadi)

O Inmetro desenvolveu e implementou modelo de avalia????o de desempenho individual, instrumento de gest??o capaz de promover nova cultura baseada no m??rito, exig??ncia, motiva????o e reconhecimento. Adota remunera????o vari??vel vinculada ao desempenho, com crit??rios objetivos e regras claras, elaborados a partir de amplo debate com os servidores; a avalia????o ?? realizada por comit??s com maioria dos membros externos ?? institui????o, rompendo com a pr??tica limitada da avalia????o exclusivamente pelas chefias. O ciclo ?? anual e o processo consta basicamente da pactua????o de um plano de trabalho do servidor com sua chefia ao in??cio do ciclo, vinculado ao conjunto de objetivos institucionais. A an??lise, ao final do ciclo, do relat??rio de atividades do servidor e do parecer de sua chefia ?? conduzida pelo Comit?? de Avalia????o. A participa????o dos servidores nos dois primeiros ciclos foi irrestrita, com excelente receptividade, independente dos resultados

Sistema e-Mec:reinven????o processual da educa????o superior em tr??s dimens??es da gest??o p??blica: jur??dica, organizacional e tecnol??gica

Com o objetivo de elevar a qualidade do ensino superior do pa??s, em 2006 o Minist??rio da Educa????o (MEC) iniciou um movimento de ???reinven????o processual??? em tr??s dimens??es: i) jur??dica, com a reformula????o da legisla????o aplic??vel aos processos regulat??rios da educa????o superior; ii) organizacional, implementando mudan??as na din??mica e no desenho das rotinas de trabalho; e iii) tecnol??gica, com a implementa????o do sistema eletr??nico e-MEC de operacionaliza????o dos procedimentos de regula????o. A tr??plice iniciativa permitiu, a um s?? tempo, trazer seguran??a jur??dica, transpar??ncia, credibilidade e celeridade ao processo. Isso possibilitou a cria????o de ambiente prop??cio ao salto qualitativo que o MEC pretendia dar em rela????o tanto ao condicionamento do funcionamento de institui????es e cursos superiores quanto ?? comprova????o da excel??ncia de sua opera????o. O objetivo final??stico foi atingido de maneira satisfat??ria, podendo-se dizer que est?? em curso a institucionaliza????o de uma cultura da qualidade da educa????o superior