RESUMEN
Tumor necrosis factor (TNF)-alpha has been implicated as a key factor in inflammatory processes occurring in erythema nodosum leprosum (ENL). In the present study, the roles of soluble factors and contact-mediated interaction in the induction of enhanced TNF-alpha secretion in leprosy have been investigated. In vitro studies have demonstrated that Mycobacterium leprae per se is a poor stimulus for TNF-alpha production by purified monocytes obtained from normal subjects, although this could be enhanced by either exogenous interferon-gamma or cell contact with fixed activated T lymphocytes. Further investigations demonstrated that monocyte-T cell contact enhanced M. leprae-induced TNF-alpha production by peripheral blood mononuclear cells of ENL patients and was modulated by blocking antibodies to CD40L, CD69, and CD18. These results suggest that physical contact with T cells isolated from patients in a particular disease state (ENL) modulates monocyte function and may contribute to the secretion of proinflammatory cytokines described in ENL.
Asunto(s)
Comunicación Celular , Monocitos/fisiología , Mycobacterium leprae/inmunología , Linfocitos T/fisiología , Factor de Necrosis Tumoral alfa/biosíntesis , Adulto , Células Cultivadas , Eritema Nudoso/inmunología , Femenino , Humanos , Lepra/inmunología , Receptores de Lipopolisacáridos/fisiología , Masculino , Persona de Mediana EdadRESUMEN
OBJECTIVE: Constant antigenic stimulation of the large immune cell population contained within gut-associated lymphoid tissue during HIV infection may contribute to patients' total viral load. The aim of this investigation was to evaluate the effect of a mucosal antigenic challenge on HIV replication. DESIGN: Prospective clinical study. METHODS: Twelve HIV-1-infected men (mean age, 42.3 years) from the Casa de Apoio Santo Antonio, Rio de Janeiro, Brazil, were immunized with combined whole cell-toxin B subunit oral cholera vaccine. Blood was collected on days 0, 2, 4, 6, 10 and 15 after immunization and plasma was tested for cholera toxin-specific antibody response (IgG and IgA), beta2-microglobulin, and plasma viral load. CD4 lymphocyte counts were performed within 1 week before immunization. Five HIV-infected non-immunized individuals were studied as controls. RESULTS: There were no adverse effects following immunization and no deterioration in clinical outcome during 3 months of follow-up. A transient increase in viral load that ranged from twofold to 60-fold was observed in all cases and was statistically significant on days 2, 6 and 10 (P = 0.017, P = 0.025, P = 0.021, respectively). There was no correlation with CD4 cell counts. None of the non-immunized subjects demonstrated the pattern of viraemia observed after immunization (P > 0.10 on all days). CONCLUSIONS: Our data indicate that mucosal immunization with oral cholera vaccine induces a transient increase in HIV viraemia, regardless of clinical stage of infection and CD4 cell counts. These findings suggest that mucosal stimulation of HIV-infected patients enhances HIV replication.
Asunto(s)
Vacunas contra el Cólera/inmunología , Infecciones por VIH/inmunología , VIH-1/fisiología , Carga Viral , Administración Oral , Adulto , Antitoxinas/sangre , Recuento de Linfocito CD4 , Toxina del Cólera/inmunología , Vacunas contra el Cólera/administración & dosificación , Infecciones por VIH/virología , Humanos , Inmunidad Mucosa , Inmunoglobulina A/sangre , Inmunoglobulina G/sangre , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Replicación Viral , Microglobulina beta-2/análisisRESUMEN
The mucosa associated lymphoid tissue regulates and coordinates immune responses against mucosal pathogens. Mucosal tissues are the major targets exposed to HIV during transmission. In this paper we describe in vitro models of HIV mucosal infection using human explants to investigate target cells within this tissue.
Asunto(s)
Adulto , Femenino , Humanos , Masculino , Cuello del Útero , Técnicas In Vitro , Infecciones por VIH/inmunología , Mucosa Intestinal , Tejido Linfoide , Inmunidad Mucosa , Membrana MucosaRESUMEN
The mucosa associated lymphoid tissue regulates and coordinates immune responses against mucosal pathogens. Mucosal tissues are the major targets exposed to HIV during transmission. In this paper we describe in vitro models of HIV mucosal infection using human explants to investigate target cells within this tissue.