RESUMO
Recent findings established that primary targets of HIV/SIV are lymphoid cells within the gastrointestinal (GI) tract. Focus has therefore shifted to T-cells expressing alpha(4)beta(7) integrin which facilitates trafficking to the GI tract via binding to MAdCAM-1. Approaches to better understand the role of alpha(4)beta(7)+ T-cells in HIV/SIV pathogenesis include their depletion or blockade of their synthesis, binding and/or homing capabilities in vivo. Such studies can ideally be conducted in rhesus macaques (RM), the non-human primate model of AIDS. Characterization of alpha(4)beta(7) expression on cell lineages in RM blood and GI tissues reveal low densities of expression by NK cells, B-cells, naïve and TEM (effector memory) T-cells. High densities were observed on TCM (central memory) T-cells. Intravenous administration of a single 50mg/kg dose of recombinant rhesus alpha(4)beta(7) antibody resulted in significant initial decline of alpha(4)beta(7)+ lymphocytes and sustained coating of the alpha(4)beta(7) receptor in both the periphery and GI tissues.
Assuntos
Anticorpos Monoclonais/imunologia , Anticorpos Monoclonais/farmacologia , Integrinas/imunologia , Síndrome de Imunodeficiência Adquirida dos Símios/imunologia , Vírus da Imunodeficiência Símia/imunologia , Animais , Anticorpos Monoclonais/sangue , Linfócitos T CD4-Positivos/efeitos dos fármacos , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD4-Positivos/virologia , Estudos Transversais , Citometria de Fluxo , Trato Gastrointestinal/efeitos dos fármacos , Trato Gastrointestinal/imunologia , Trato Gastrointestinal/virologia , Integrinas/biossíntese , Estudos Longitudinais , Macaca mulatta , Masculino , Projetos Piloto , RNA Viral/química , RNA Viral/genética , Proteínas Recombinantes/sangue , Proteínas Recombinantes/imunologia , Proteínas Recombinantes/farmacologia , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Síndrome de Imunodeficiência Adquirida dos Símios/sangue , Síndrome de Imunodeficiência Adquirida dos Símios/virologia , Vírus da Imunodeficiência Símia/genética , Subpopulações de Linfócitos T/efeitos dos fármacos , Subpopulações de Linfócitos T/imunologia , Subpopulações de Linfócitos T/virologia , Tretinoína/farmacologia , Carga ViralRESUMO
BACKGROUND: Nosocomial outbreaks of parvovirus B19 (pB19) have been reported, but they rarely occur among healthcare personnel (HCP). Susceptibility among pregnant HCP was the major concern. METHODS: An outbreak of pB19 among HCP is described in a paediatric ward with a cross-sectional serologic study in all HCP and patients exposed to the outbreak. Acute infection was diagnosed by polymerase chain reaction or positive anti-parvovirus B19 IgM. FINDINGS: Among 48 HCP (three pregnant) and 22 patients included in the outbreak serologic study, 11 (23%) HCP and two (9%) patients had acute infection. Of these, six HCP and no patients were symptomatic. Clinical manifestations included itchy rash (100%) and joint pain following resolution of rash (67%), with median rash duration of four days. Forty percent of HCP and 50% of patients had positive anti-parvovirus IgG, indicating previously immune status. HCP with acute infection and HCP who were susceptible without infection were younger than HCP with previous immunity (mean age 32.2 vs 40.5 years, respectively; P = 0.003). The attack rate was 38% among HCP and 18% among patients who were susceptible, respectively. The outbreak ended within two weeks following strict droplet precaution and segregation of symptomatic HCP. CONCLUSION: Parvovirus B19 infection may cause nosocomial outbreak with high attack rate among HCP. Outbreak control with droplet precaution was highly effective.
Assuntos
Infecção Hospitalar/epidemiologia , Surtos de Doenças , Eritema Infeccioso/epidemiologia , Pessoal de Saúde , Hospitais Pediátricos , Parvovirus B19 Humano/isolamento & purificação , Adulto , Anticorpos Antivirais/sangue , Pré-Escolar , Estudos Transversais , DNA Viral/sangue , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Imunoglobulina M/sangue , Lactente , Recém-Nascido , Masculino , Reação em Cadeia da Polimerase , Centros de Atenção Terciária , Tailândia/epidemiologia , Adulto JovemRESUMO
Differences in clinical outcome of simian immunodeficiency virus (SIV) infection in disease-resistant African sooty mangabeys (SM) and disease-susceptible Asian rhesus macaques (RM) prompted us to examine the role of regulatory T cells (Tregs) in these two animal models. Results from a cross-sectional study revealed maintenance of the frequency and absolute number of peripheral Tregs in chronically SIV-infected SM while a significant loss occurred in chronically SIV-infected RM compared to uninfected animals. A longitudinal study of experimentally SIV-infected animals revealed a transient increase in the frequency of Tregs from baseline values following acute infection in RM, but no change in the frequency of Tregs occurred in SM during this period. Further examination revealed a strong correlation between plasma viral load (VL) and the level of Tregs in SIV-infected RM but not SM. A correlation was also noted in SIV-infected RM that control VL spontaneously or in response to antiretroviral chemotherapy. In addition, immunofluorescent cell count assays showed that while Treg-depleted peripheral blood mononuclear cells from RM led to a significant enhancement of CD4+ and CD8+ T-cell responses to select pools of SIV peptides, there was no detectable T-cell response to the same pool of SIV peptides in Treg-depleted cells from SIV-infected SM. Our data collectively suggest that while Tregs do appear to play a role in the control of viremia and the magnitude of the SIV-specific immune response in RM, their role in disease resistance in SM remains unclear.