RESUMEN
BACKGROUND: The irritable bowel syndrome (IBS) is a functional gastrointestinal disorder whose pathogenesis is not completely understood. Its high prevalence and the considerable effects on quality of life make IBS a disease with high social cost. Recent studies suggest that low grade mucosal immune activation, increased intestinal permeability and the altered host-microbiota interactions that modulate innate immune response, contribute to the pathophysiology of IBS. However, the understanding of the precise molecular pathophysiology remains largely unknown. METHODOLOGY AND FINDINGS: In this study our objective was to evaluate the TLR expression as a key player in the innate immune response, in the colonic mucosa of IBS patients classified into the three main subtypes (with constipation, with diarrhea or mixed). TLR2 and TLR4 mRNA expression was assessed by real time RT-PCR while TLRs protein expression in intestinal epithelial cells was specifically assessed by flow cytometry and immunofluorescence. Mucosal inflammatory cytokine production was investigated by the multiplex technology. Here we report that the IBS-Mixed subgroup displayed a significant up-regulation of TLR2 and TLR4 in the colonic mucosa. Furthermore, these expressions were localized in the epithelial cells, opening new perspectives for a potential role of epithelial cells in host-immune interactions in IBS. In addition, the increased TLR expression in IBS-M patients elicited intracellular signaling pathways resulting in increased expression of the mucosal proinflammatory cytokines IL-8 and IL1ß. CONCLUSIONS: Our results provide the first evidence of differential expression of TLR in IBS patients according to the disease subtype. These results offer further support that microflora plays a central role in the complex pathophysiology of IBS providing novel pharmacological targets for this chronic gastrointestinal disorder according to bowel habits.
Asunto(s)
Colon/metabolismo , Mucosa Intestinal/metabolismo , Síndrome del Colon Irritable/metabolismo , Receptor Toll-Like 2/metabolismo , Receptor Toll-Like 4/metabolismo , Adulto , Anciano , Estudios de Casos y Controles , Colon/inmunología , Colon/patología , Citocinas/metabolismo , Femenino , Expresión Génica , Humanos , Mediadores de Inflamación/metabolismo , Mucosa Intestinal/inmunología , Mucosa Intestinal/patología , Síndrome del Colon Irritable/inmunología , Síndrome del Colon Irritable/patología , Receptores de Lipopolisacáridos/metabolismo , Masculino , Persona de Mediana Edad , PPAR gamma/metabolismo , ARN Mensajero/genética , ARN Mensajero/metabolismo , Receptor Toll-Like 2/genética , Receptor Toll-Like 4/genética , Regulación hacia ArribaRESUMEN
Mucosal surfaces play a major role in human immunodeficiency virus type 1 (HIV-1) transmission and pathogenesis. Since the role of intestinal macrophages as viral reservoirs during chronic HIV-1 infection has not been elucidated, we investigated the effects of successful therapy on intestinal HIV-1 persistence. Intestinal macrophage infection was demonstrated by the expression of p24 antigen by flow cytometry and by the presence of proviral DNA, assessed by PCR. Proviral DNA was detected in duodenal mucosa of HIV-infected patients under treatment with undetectable plasma viral load. These findings confirm that intestinal macrophages can act as viral reservoirs and permit HIV-1 production even after viral suppression following antiretroviral therapy.
Asunto(s)
Terapia Antirretroviral Altamente Activa/métodos , Duodeno/virología , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/virología , VIH-1/aislamiento & purificación , VIH-1/patogenicidad , Macrófagos/virología , ADN Viral/análisis , Femenino , Citometría de Flujo , Proteína p24 del Núcleo del VIH/análisis , Humanos , Masculino , Reacción en Cadena de la Polimerasa , Provirus/genéticaRESUMEN
Survival of lymphocytes after prolonged culture was studied in two asymptomatic XLP patients. Viability of XLP PBMC after 30 days of non-stimulated culture was higher than that of normal controls (N), mainly due to the persistence of CD8 memory lymphocytes. IFNgamma high CD8 T lymphocytes remained higher in XLP than in N after 30 days. The number of perforin+ CD8 lymphocytes was markedly reduced after 30 days in XLP and in N. Increased viability was not related to CD127, PD-1, CD27, or CD62L expression. Concerning B lymphocytes, memory CD27+ CD19+ cells prevailed over CD27- cells after 30 days in both XLP and N, with far more surviving cells in XLP. In N, few CD19+ B lymphocytes were viable after prolonged culture. In XLP, these cells were also IgD+, IgM+ and EBNA2+. These results demonstrate that IFNgamma-positive memory CD8 T cells persist in XLP after prolonged culture in association with a subset of viable memory CD27+ B cells expressing latent EBV antigens. The survival advantage of XLP cells might be related to increased frequency of extranodal lymphoma in XLP patients.
Asunto(s)
Linfocitos B/patología , Linfocitos T CD4-Positivos/patología , Linfocitos T CD8-positivos/patología , Péptidos y Proteínas de Señalización Intracelular/metabolismo , Trastornos Linfoproliferativos/patología , Adulto , Antígenos CD/metabolismo , Proteínas Reguladoras de la Apoptosis/metabolismo , Linfocitos B/inmunología , Linfocitos B/virología , Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD4-Positivos/virología , Linfocitos T CD8-positivos/inmunología , Linfocitos T CD8-positivos/virología , Supervivencia Celular , Células Cultivadas , Cromosomas Humanos X/genética , Infecciones por Virus de Epstein-Barr/complicaciones , Humanos , Interferón gamma/metabolismo , Subunidad alfa del Receptor de Interleucina-7/metabolismo , Péptidos y Proteínas de Señalización Intracelular/genética , Trastornos Linfoproliferativos/inmunología , Trastornos Linfoproliferativos/virología , Perforina/metabolismo , Receptor de Muerte Celular Programada 1 , Proteína Asociada a la Molécula de Señalización de la Activación LinfocitariaRESUMEN
The presence of HIV-1 RNA in distal duodenal mucosa was evaluated in 44 HIV-1-positive patients. HIV-1 RNA was detected in gut tissue in antiretroviral-naive patients with high plasma viral loads, as well as in patients on HAART with plasma viral loads below the limit of detection and in patients on HAART with virological failure. The intestinal mucosa seems to serve as a reservoir poorly influenced by levels of plasma viral load or HAART.
Asunto(s)
Terapia Antirretroviral Altamente Activa , Infecciones por VIH/virología , VIH-1/aislamiento & purificación , Mucosa Intestinal/virología , ARN Viral/sangre , Adulto , Femenino , Infecciones por VIH/tratamiento farmacológico , Humanos , Masculino , Resultado del Tratamiento , Carga ViralRESUMEN
Dendritic cells are most important as antigen presenting cells during the induction of an effective immune response. Therefore, it is important to study their role during the generation of persistent or chronic viral infections, such as HIV or HCV infection. In this review we shall describe the phenotypic and functional characteristics of the different classes of dendritic cells and of their membrane receptors. Their participation in defence or facilitation mechanisms involved in the immune response against these viruses will be discussed. It is important to take this knowledge into account when trying to design therapeutic strategies for protection or reconstruction of the immune system that may be altered as a consequence of infection with HIV or HCV.
Asunto(s)
Células Dendríticas/inmunología , Infecciones por VIH/inmunología , Hepatitis C Crónica/inmunología , Diferenciación Celular , Linaje de la Célula/inmunología , Citocinas/inmunología , Células Dendríticas/citología , VIH/inmunología , Hepacivirus/inmunología , Humanos , Inmunidad Celular , Linfocitos T/inmunología , Receptores Toll-Like/inmunología , Acoplamiento Viral , Internalización del VirusRESUMEN
Human immune deficiency virus (HIV) and human hepatitis C virus (HCV) infection are frequent in patients who have been exposed to blood or blood-derived products. It has been suggested that HIV infection increases HCV replication altering the course of HCV-related disease. However, it is not known if HIV directly enhances HCV replication or if its effect is the consequence of HIV infection of other cell types that control HCV replication (lymphocytes, macrophages). While the main cell targets for HIV infection are mononuclear leukocytes bearing CD4 and the chemokine receptors CCR5 and CXCR4, HCV was originally thought to be strictly hepatotropic, but it is now known that HCV can also replicate in peripheral blood mononuclear cells (PBMC). Therefore, in co-infected individuals, these two different viruses could share cell targets and interact either directly or indirectly. Some membrane receptors can be used by both HCV and HIV for entry into target cells, but the intracellular mechanisms shared by these viruses are not known. Lack of experimental systems providing suitable methods for the study of HCV replication in the presence or absence of HIV co-infection has hampered advances in this research area, but recent investigations are currently going on in order to answer these questions. This is an important issue, as knowledge of HIV/HCV interactions is required for the design of effective antiviral therapies.
Asunto(s)
Infecciones por VIH/inmunología , Hepatitis C/inmunología , Replicación Viral , Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD8-positivos/inmunología , Células Dendríticas/fisiología , Células Dendríticas/virología , Infecciones por VIH/virología , Hepacivirus/fisiología , HumanosRESUMEN
Las células dendríticas son las principales células presentadoras de antígenos para el montaje de la respuesta inmune. Por lo tanto es importante estudiar de qué manera intervienen en el equilibrio que el sistema inmune desarrolla frente a infecciones virales persistentes como la infección por el HIV o el HCV. En esta revisión se presentan en primer término generalidades sobre las diferentes clases de células dendríticas, las características fenotípicas y funcionales que las definen y los receptores que pueden estar involucrados en la infección viral. Luego se analiza su participación en los mecanismos de defensa o facilitadores de la infección por estos virus. Es importante tener en cuenta estos conocimientos para poder diseñar adecuadas estrategias de vacunación o protección y para intentar la reconstrucción funcional del sistema inmune impidiendo la subversión de los mecanismos inmunes de defensa causada por la infección con el HIV y el HCV.(AU)
Dendritic cells are most important as antigen presenting cells during the induction of an effective immune response. Therefore, it is important to study their role during the generation of persistent or chronic viral infections, such as HIV or HCV infection. In this review we shall describe the phenotypic and functional characteristics of the different classes of dendritic cells and of their membrane receptors. Their participation in defence or facilitation mechanisms involved in the immune response against these viruses will be discussed. It is important to take this knowledge into account when trying to design therapeutic strategies for protection or reconstruction of the immune system that may be altered as a consequence of infection with HIV or HCV. (AU)
Asunto(s)
Humanos , Infecciones por VIH/inmunología , Células Dendríticas/inmunología , Hepatitis C Crónica/inmunología , Células Dendríticas/citología , Diferenciación Celular , Linfocitos T/inmunología , Receptores Toll-Like/inmunología , Linaje de la Célula/inmunología , Citocinas/inmunologíaRESUMEN
Las células dendríticas son las principales células presentadoras de antígenos para el montaje de la respuesta inmune. Por lo tanto es importante estudiar de qué manera intervienen en el equilibrio que el sistema inmune desarrolla frente a infecciones virales persistentes como la infección por el HIV o el HCV. En esta revisión se presentan en primer término generalidades sobre las diferentes clases de células dendríticas, las características fenotípicas y funcionales que las definen y los receptores que pueden estar involucrados en la infección viral. Luego se analiza su participación en los mecanismos de defensa o facilitadores de la infección por estos virus. Es importante tener en cuenta estos conocimientos para poder diseñar adecuadas estrategias de vacunación o protección y para intentar la reconstrucción funcional del sistema inmune impidiendo la subversión de los mecanismos inmunes de defensa causada por la infección con el HIV y el HCV.
Dendritic cells are most important as antigen presenting cells during the induction of an effective immune response. Therefore, it is important to study their role during the generation of persistent or chronic viral infections, such as HIV or HCV infection. In this review we shall describe the phenotypic and functional characteristics of the different classes of dendritic cells and of their membrane receptors. Their participation in defence or facilitation mechanisms involved in the immune response against these viruses will be discussed. It is important to take this knowledge into account when trying to design therapeutic strategies for protection or reconstruction of the immune system that may be altered as a consequence of infection with HIV or HCV.
Asunto(s)
Humanos , Células Dendríticas/inmunología , Infecciones por VIH/inmunología , Hepatitis C Crónica/inmunología , Diferenciación Celular , Linaje de la Célula/inmunología , Citocinas/inmunología , Células Dendríticas/citología , Linfocitos T/inmunología , Receptores Toll-Like/inmunologíaRESUMEN
In order to investigate hepatitis C virus (HCV) persistence and replication in peripheral blood mononuclear cells (PBMC) from a group of haemophilic individuals, HCV production and release to PBMC culture supernatants (SNs) from HCV singly infected patients and HIV/HCV co-infected patients was studied. HCV RNA+ SNs were found more frequently from HIV/HCV co-infected individuals (89.5 %) with poor reconstitution of their immune status than from singly HCV-infected patients (57 %) or from HIV/HCV co-infected individuals with a good response to highly active anti-retroviral therapy (50 %). The presence of the HCV genome in culture SNs was associated with lower CD4+ T-cell counts and with a more severe clinical picture of HIV infection. In spite of prolonged negative HCV viraemia, PBMC from HIV/HCV co-infected patients released the HCV genome after culture. HCV permissive PBMC allowed generation of HCV productive B cell lines with continuous HCV replication. These findings add further weight to the involvement of PBMCs in persistence of HCV infection and emphasize the role of B lymphocytes as HCV reservoirs.
Asunto(s)
Hepacivirus/aislamiento & purificación , Hepatitis C Crónica/virología , Leucocitos Mononucleares/virología , Fármacos Anti-VIH/uso terapéutico , Terapia Antirretroviral Altamente Activa , Linfocitos B/virología , Recuento de Linfocito CD4 , Línea Celular Tumoral/virología , Células Cultivadas , Infecciones por VIH/complicaciones , Infecciones por VIH/tratamiento farmacológico , Hepacivirus/genética , Hepatitis C Crónica/complicaciones , Hepatitis C Crónica/inmunología , Humanos , ARN Viral/análisis , Factores de TiempoRESUMEN
In addition to the CD4 molecule that binds to the human immunodeficiency virus type-1 (HIV-1) envelope glycoprotein gp120, productive HIV-1 infection requires interaction with cellular receptors for alpha- or beta- chemokines (CXCR4 and CCR5 respectively). Isolates of HIV-1 exhibit different tropism depending on the chemokine receptor type that they use to infect their cellular targets. HIV-1 strains that use preferentially CCR5 are known as R5 strains. They are more frequently found in asymptomatic individuals during the initial stages of the disease and are involved in the transmision of infection from mother to child. HIV-1 species using CXCR4 (X4 strains) are observed mainly in patients with advanced disease. While X4 isolates are associated with syncitium formation, in general R5 strains are not. Interaction of X4 and R5 with their specific receptors is necessary to establish productive HIV-1 infection and trigger a series of intracellular signals. Modulation of CXCR4 and CCR5 expression after HIV-1 infection is one of the results of such interaction and may have important consequences on the course of the infection. Down regulation of CCR5 and CXCR4 after HIV-1 infection could be the result of indirect events linked to HIV-1 infection, such as the induction of alpha- or beta-chemokines competing with the virions for receptor binding. They could also reflect direct effects of HIV-1 on chemokine-receptor turnover. In this review, the mechanisms of modulation of CXCR4 and CCR5 expression after HIV-1 infection will be discussed.
Asunto(s)
Regulación de la Expresión Génica , Infecciones por VIH/virología , VIH-1/inmunología , VIH-1/fisiología , Receptores CCR5/metabolismo , Receptores CXCR4/metabolismo , Receptores del VIH/metabolismo , Quimiocinas CC/metabolismo , Quimiocinas CXC/metabolismo , Regulación hacia Abajo , Proteína gp120 de Envoltorio del VIH/fisiología , Proteína gp41 de Envoltorio del VIH/fisiología , Humanos , Receptores CCR5/genética , Receptores CCR5/inmunología , Receptores CXCR4/genética , Receptores CXCR4/inmunología , Receptores del VIH/genética , Receptores del VIH/inmunologíaRESUMEN
Production of the Th1 cytokine IFN-gamma by T cells is considered crucial for immunity against Mycobacterium tuberculosis infection. We evaluated IFN-gamma production in tuberculosis in the context of signaling molecules known to regulate Th1 cytokines. Two populations of patients who have active tuberculosis were identified, based on their T cell responses to the bacterium. High responder tuberculosis patients displayed significant M. tuberculosis-dependent T cell proliferation and IFN-gamma production, whereas low responder tuberculosis patients displayed weak or no T cell responses to M. tuberculosis. The expression of the signaling lymphocytic activation molecule (SLAM)-associated protein (SAP) on cells from tuberculosis patients was inversely correlated with IFN-gamma production in those individuals. Moreover, patients with a nonfunctional SAP gene displayed immune responses to M. tuberculosis similar to those of high responder tuberculosis patients. In contrast to SAP, T cell expression of SLAM was directly correlated with responsiveness to M. tuberculosis Ag. Our data suggest that expression of SAP interferes with Th1 responses whereas SLAM expression contributes to Th1 cytokine responses in tuberculosis. The study further suggests that SAP and SLAM might be focal points for therapeutic modulation of T cell cytokine responses in tuberculosis.
Asunto(s)
Proteínas Portadoras/biosíntesis , Regulación hacia Abajo/inmunología , Glicoproteínas/metabolismo , Inmunoglobulinas/metabolismo , Interferón gamma/antagonistas & inhibidores , Interferón gamma/biosíntesis , Péptidos y Proteínas de Señalización Intracelular , Tuberculosis/inmunología , Adyuvantes Inmunológicos/metabolismo , Adyuvantes Inmunológicos/fisiología , Anticuerpos Monoclonales/metabolismo , Antígenos CD , Proteínas Portadoras/genética , Proteínas Portadoras/metabolismo , Proteínas Portadoras/fisiología , Células Cultivadas , Cromosomas Humanos X/inmunología , Glicoproteínas/fisiología , Humanos , Inmunidad Celular/genética , Inmunoglobulinas/fisiología , Interferón gamma/farmacología , Interleucina-12/farmacología , Ligandos , Trastornos Linfoproliferativos/genética , Trastornos Linfoproliferativos/inmunología , Mycobacterium tuberculosis/inmunología , Receptores de Superficie Celular , Índice de Severidad de la Enfermedad , Transducción de Señal/genética , Transducción de Señal/inmunología , Proteína Asociada a la Molécula de Señalización de la Activación Linfocitaria , Miembro 1 de la Familia de Moléculas Señalizadoras de la Activación Linfocitaria , Tuberculosis/genética , Tuberculosis/microbiología , Regulación hacia Arriba/inmunologíaRESUMEN
Detailed longitudinal studies of patients with X-linked lymphoproliferative disease (XLP) may increase our understanding of the immunologic defects that contribute to the development of lymphoma and hypogammaglobulinemia in XLP. We describe progressive changes observed in immunoglobulin concentrations, lymphocyte subsets, and Epstein-Barr virus (EBV) loads occurring in a 2-year period in a newly infected, but otherwise healthy, carrier (patient 9). We compare these findings with those observed in the patient's brother, who had hypogammaglobulinemia and XLP (patient 4). Immunoglobulin G (IgG), IgM, and IgA concentrations increased in patient 9 during acute EBV infection, but thereafter they decreased steadily to concentrations consistent with hypogammaglobulinemia, reaching a plateau 5 months after infection. In both patients, CD19+ B-lymphocyte rates remained lower than 3%, with a contraction of the B-cell memory compartment (CD27+ CD19+/CD19+) to 20% (normal range, 32%-56%). T-lymphocyte subpopulations showed a reduction in CD4+ T-cell counts and a permanent CD8+ T-cell expansion. Interestingly, CXCR3 memory TH1 cells were expanded and CCR4+ TH2 lymphocytes were reduced, suggesting that abnormal skewing of memory T-cell subsets might contribute to reduced antibody synthesis. Despite an expanded number of CD3+CD8+ lymphocytes, increased EBV loads occurred in both patients without overt clinical symptoms of mononucleosis, lymphoproliferative disease, or lymphoma.
Asunto(s)
Linfocitos B/metabolismo , Infecciones por Virus de Epstein-Barr/sangre , Herpesvirus Humano 4/metabolismo , Trastornos Linfoproliferativos/virología , Receptores de Quimiocina/biosíntesis , Linfocitos T/metabolismo , Miembro 7 de la Superfamilia de Receptores de Factores de Necrosis Tumoral/biosíntesis , Adulto , Antígenos CD19/biosíntesis , Complejo CD3/biosíntesis , Antígenos CD8/biosíntesis , Niño , Preescolar , Salud de la Familia , Humanos , Inmunoglobulina A/metabolismo , Inmunoglobulina G/metabolismo , Inmunoglobulina M/metabolismo , Memoria Inmunológica , Inmunofenotipificación , Linfoma/complicaciones , Trastornos Linfoproliferativos/genética , Masculino , Linaje , Polimorfismo de Longitud del Fragmento de Restricción , Receptores CCR4 , Receptores CXCR3 , Factores de TiempoRESUMEN
Mutations in SH2D1A, a gene that codifies for the regulatory protein SAP, result in uncontrolled activation of the SLAM (signaling lymphocyte-activation molecule) pathway. This X-linked immunodeficiency becomes evident when the patients are infected with Epstein Barr virus (EBV) and develop a fulminant form of infectious mononucleosis leading to a lymphoproliferative syndrome that is often fatal (X-linked lymphoproliferative syndrome, XLP). In those who survive, hypogammaglobulinemia and oncohematologic diseases are frequently observed. In this revision, the immuno-regulatory mechanisms involved in XLP immunopathology and the role of different effector cells (CD8 T lymphocytes, NK cells) are discussed.
Asunto(s)
Proteínas Portadoras/genética , Infecciones por Virus de Epstein-Barr/genética , Glicoproteínas/genética , Inmunoglobulinas/genética , Péptidos y Proteínas de Señalización Intracelular , Trastornos Linfoproliferativos/genética , Linfocitos T Citotóxicos/inmunología , Antígenos CD , Citotoxicidad Inmunológica , Infecciones por Virus de Epstein-Barr/inmunología , Herpesvirus Humano 4/inmunología , Humanos , Células Asesinas Naturales/inmunología , Trastornos Linfoproliferativos/inmunología , Receptores de Superficie Celular , Proteína Asociada a la Molécula de Señalización de la Activación Linfocitaria , Miembro 1 de la Familia de Moléculas Señalizadoras de la Activación LinfocitariaRESUMEN
Mutations in SH2D1A, a gene that codifies for the regulatory protein SAP, result in uncontrolled activation of the SLAM (signaling lymphocyte-activation molecule) pathway. This X-linked immunodeficiency becomes evident when the patients are infected with Epstein Barr virus (EBV) and develop a fulminant form of infectious mononucleosis leading to a lymphoproliferative syndrome that is often fatal (X-linked lymphoproliferative syndrome, XLP). In those who survive, hypogammaglobulinemia and oncohematologic diseases are frequently observed. In this revision, the immuno-regulatory mechanisms involved in XLP immunopathology and the role of different effector cells (CD8 T lymphocytes, NK cells) are discussed (AU)
Asunto(s)
RESEARCH SUPPORT, NON-U.S. GOVT , Humanos , Cromosoma X , Infecciones por Virus de Epstein-Barr/genética , Linfocitos T Citotóxicos/inmunología , Glicoproteínas/genética , Trastornos Linfoproliferativos/genética , Proteínas Portadoras/genética , Herpesvirus Humano 4/inmunología , Infecciones por Virus de Epstein-Barr/inmunología , Pruebas Inmunológicas de Citotoxicidad , Trastornos Linfoproliferativos/inmunología , Células Asesinas Naturales/inmunologíaRESUMEN
Mutations in SH2D1A, a gene that codifies for the regulatory protein SAP, result in uncontrolled activation of the SLAM (signaling lymphocyte-activation molecule) pathway. This X-linked immunodeficiency becomes evident when the patients are infected with Epstein Barr virus (EBV) and develop a fulminant form of infectious mononucleosis leading to a lymphoproliferative syndrome that is often fatal (X-linked lymphoproliferative syndrome, XLP). In those who survive, hypogammaglobulinemia and oncohematologic diseases are frequently observed. In this revision, the immuno-regulatory mechanisms involved in XLP immunopathology and the role of different effector cells (CD8 T lymphocytes, NK cells) are discussed
Asunto(s)
Humanos , Proteínas Portadoras , Infecciones por Virus de Epstein-Barr , Glicoproteínas , Trastornos Linfoproliferativos , Linfocitos T Citotóxicos , Cromosoma X , Pruebas Inmunológicas de Citotoxicidad , Infecciones por Virus de Epstein-Barr , Herpesvirus Humano 4 , Células Asesinas Naturales , Trastornos LinfoproliferativosRESUMEN
Mutations in SH2D1A, a gene that codifies for the regulatory protein SAP, result in uncontrolled activation of the SLAM (signaling lymphocyte-activation molecule) pathway. This X-linked immunodeficiency becomes evident when the patients are infected with Epstein Barr virus (EBV) and develop a fulminant form of infectious mononucleosis leading to a lymphoproliferative syndrome that is often fatal (X-linked lymphoproliferative syndrome, XLP). In those who survive, hypogammaglobulinemia and oncohematologic diseases are frequently observed. In this revision, the immuno-regulatory mechanisms involved in XLP immunopathology and the role of different effector cells (CD8 T lymphocytes, NK cells) are discussed.
RESUMEN
We studied the release of p24 antigen from peripheral blood mononuclear cell-derived monocyte/macrophages obtained from 13 HIV-positive patients receiving highly active antiretroviral therapy (HAART). Although HIV-infected monocyte/macrophages were detected in 80% of patients after 36 months of continuous treatment, additional exposure to HAART reduced the chance of detecting HIV-releasing monocyte/macrophages. Therefore, after more than 3 years of HAART, recently infected monocytes may play a less important role as a source of emerging HIV-1 upon HAART interruption.
Asunto(s)
Fármacos Anti-VIH/uso terapéutico , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/virología , VIH-1/aislamiento & purificación , VIH-1/fisiología , Leucocitos Mononucleares/virología , Macrófagos/virología , Replicación Viral , Fármacos Anti-VIH/administración & dosificación , Terapia Antirretroviral Altamente Activa , Humanos , Factores de TiempoRESUMEN
Luego del tratamiento anti-retroviral combinado de alta eficacia, la mayoría de los pacientes HIV+ recuperan los niveles de linfocitos T CD4+ y reducen la carga viral plasmática, a veces a niveles inferiores a los detectables con métodos de gran sensibilidad. Sin embargo, al interrumpir el tratamiento, los valores de CD4 caen, los niveles de carga viral retornan a los observados antes del tratamiento y no se conoce la fuente del virus re-emergente. Por un lado se reconoce la existencia de reservorios de virus latente en células CD4 de memoria en reposo. Además se ha demostrado la replicación continua de HIV, en tejidos en los cuales la concentración de los antiretrovirales es subóptima. Se presenta un sistema de cultivo prolongado sin estímulo de los leucocitos mononucleares de sangre periférica que puede ser útil para detectar el "pool" de células con replicación residual. Mediante este sistema se demostró que es posible recuperar virus infectivo a partir de los monocitos de sangre periférica de pacientes HIV+ que han recibido hasta 3 años de tratamiento anti-retroviral combinado no interrumpido. Los niveles de este reservorio caen después de tiempos más prolongados de tratamiento, lo que sugiere que es posible reducir esta fuente de virus re-emergente. (AU)
Asunto(s)
Humanos , Macrófagos/inmunología , VIH , Infecciones por VIH/terapia , Infecciones por VIH/virología , Terapia Combinada/métodos , Leucocitos Mononucleares , Linfocitos T CD4-Positivos , Replicación Viral/efectos de los fármacos , Replicación Viral/genética , Citometría de FlujoRESUMEN
Luego del tratamiento anti-retroviral combinado de alta eficacia, la mayoría de los pacientes HIV+ recuperan los niveles de linfocitos T CD4+ y reducen la carga viral plasmática, a veces a niveles inferiores a los detectables con métodos de gran sensibilidad. Sin embargo, al interrumpir el tratamiento, los valores de CD4 caen, los niveles de carga viral retornan a los observados antes del tratamiento y no se conoce la fuente del virus re-emergente. Por un lado se reconoce la existencia de reservorios de virus latente en células CD4 de memoria en reposo. Además se ha demostrado la replicación continua de HIV, en tejidos en los cuales la concentración de los antiretrovirales es subóptima. Se presenta un sistema de cultivo prolongado sin estímulo de los leucocitos mononucleares de sangre periférica que puede ser útil para detectar el "pool" de células con replicación residual. Mediante este sistema se demostró que es posible recuperar virus infectivo a partir de los monocitos de sangre periférica de pacientes HIV+ que han recibido hasta 3 años de tratamiento anti-retroviral combinado no interrumpido. Los niveles de este reservorio caen después de tiempos más prolongados de tratamiento, lo que sugiere que es posible reducir esta fuente de virus re-emergente.
Asunto(s)
Humanos , Linfocitos T CD4-Positivos , Terapia Combinada , VIH , Infecciones por VIH , Leucocitos Mononucleares , Macrófagos/inmunología , Replicación Viral , Replicación Viral/genética , Citometría de FlujoRESUMEN
Se estudiaron variaciones en la expresión de los co-receptores CXCR4 y CCR5 luego del cultivo no estimulado de LM de pacientes VIH+ por periodos de 3 a 20 días. El porcentaje de células CCR5+ descendió tanto en linfocitos T CD4+ como en T CD8+ luego de 7 días, manteniéndose disminuido hasta los 20 días. En cambio los niveles de CXCR4 se mantuvieron estables durante el cultivo en ambas subpoblaciones. En los cultivos de LM de donantes VIH- no hubo cambios significativos en la expresión de CCR5 ni en la de CXCR4. Para comprobar si la disminución de CCR5 estaba asociada a la replicación viral, se infectaron LM VIH- (pre-cultivados por 6 días) con sobrenadantes de cultivos de LM VIH+. Luego de 3 días de infección, la expresión de CCR5 se redujo tanto en linfocitos T CD4+ como en linfocitos T CD8+ , coincidiendo con la replicación viral durante el cultivo. (AU)