Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 5 de 5
Filtrar
Más filtros












Base de datos
Intervalo de año de publicación
1.
J Autoimmun ; 135: 102994, 2023 02.
Artículo en Inglés | MEDLINE | ID: mdl-36706535

RESUMEN

In rheumatoid arthritis, the emergence of anti-citrullinated autoimmunity is associated with HLA-antigen-T cell receptor complexes. The precise mechanisms underpinning this breach of tolerance are not well understood. Porphyromonas gingivalis expresses an enzyme capable of non-endogenous C-terminal citrullination with potential to generate citrullinated autoantigens. Here we document how C-terminal citrullination of ovalbumin peptide323-339 alters the interaction between antigen-presenting cells and OTII T cells to induce functional changes in responding T cells. These data reveal that C-terminal citrullination is sufficient to breach T cell peripheral tolerance in vivo and reveal the potential of C-terminal citrullination to lower the threshold for T cell activation. Finally, we demonstrate a role for the IL-2/STAT5/CD25 signalling axis in breach of tolerance. Together, our data identify a tractable mechanism and targetable pathways underpinning breach of tolerance in rheumatoid arthritis and provide new conceptual insight into the origins of anti-citrullinated autoimmunity.


Asunto(s)
Artritis Reumatoide , Citrulina , Humanos , Tolerancia Inmunológica , Péptidos , Comunicación Celular
2.
Br J Pharmacol ; 159(4): 808-11, 2010 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-20015295

RESUMEN

BACKGROUND AND PURPOSE: T-cells may play a role in the evolution of ischaemic damage and repair, but the ability to image these cells in the living brain after a stroke has been limited. We aim to extend the technique of real-time in situ brain imaging of T-cells, previously shown in models of immunological diseases, to models of experimental stroke. EXPERIMENTAL APPROACH: Male C57BL6 mice (6-8 weeks) (n= 3) received a total of 2-5 x 10(6) carboxyfluorescein diacetate succinimidyl ester (CFSE)-labelled lymphocytes from donor C57BL6 mice via i.v. injection by adoptive transfer. Twenty-four hours later, recipient mice underwent permanent left distal middle cerebral artery occlusion (MCAO) by electrocoagulation or by sham surgery under isoflurane anaesthesia. Female hCD2-green fluorescent protein (GFP) transgenic mice that exhibit GFP-labelled T-cells underwent MCAO. At 24 or 48 h post-MCAO, a sagittal brain slice (1500 microm thick) containing cortical branches of the occluded middle cerebral artery (MCA) was dissected and used for multiphoton laser scanning microscopy (MPLSM). KEY RESULTS: Our results provide direct observations for the first time of dynamic T-cell behaviour in living brain tissue in real time and herein proved the feasibility of MPLSM for ex vivo live imaging of immune response after experimental stroke. CONCLUSIONS AND IMPLICATIONS: It is hoped that these advances in the imaging of immune cells will provide information that can be harnessed to a therapeutic advantage.


Asunto(s)
Encéfalo/metabolismo , Infarto de la Arteria Cerebral Media/metabolismo , Microscopía de Fluorescencia por Excitación Multifotónica , Imagen Molecular , Técnicas de Sonda Molecular , Linfocitos T/metabolismo , Traslado Adoptivo , Animales , Encéfalo/inmunología , Modelos Animales de Enfermedad , Estudios de Factibilidad , Femenino , Fluoresceínas/metabolismo , Colorantes Fluorescentes/metabolismo , Proteínas Fluorescentes Verdes/genética , Proteínas Fluorescentes Verdes/metabolismo , Infarto de la Arteria Cerebral Media/inmunología , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Transgénicos , Succinimidas/metabolismo , Linfocitos T/inmunología , Linfocitos T/trasplante , Factores de Tiempo
3.
Parasite Immunol ; 31(3): 147-50, 2009 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-19222786

RESUMEN

T-cells are known to play a role in the pathology associated with experimental cerebral malaria, although it has not previously been possible to examine their behaviour in brain. Using multiphoton laser scanning microscopy, we have examined the migration and movement of these cells in brain tissue. We believe that this approach will help define host-parasite interactions and examine how intervening in these relationships affects the development of cerebral pathology.


Asunto(s)
Encéfalo/inmunología , Encéfalo/patología , Movimiento Celular/inmunología , Malaria Cerebral/inmunología , Malaria Cerebral/patología , Microscopía Confocal/métodos , Linfocitos T/inmunología , Animales , Ratones
4.
Parasite Immunol ; 30(4): 223-33, 2008 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-18324925

RESUMEN

Malaria infects 500 million people and kills an estimated 2.7 million annually, representing one of the most significant diseases in the world. However, efforts to develop effective vaccines have met with limited success. One reason is our lack of basic knowledge of how and where the immune system responds to parasite antigens. This is important as the early events during induction of an immune response influence the acquisition of effector function and development of memory responses. Our knowledge of the interactions of Plasmodia with the host immune system has largely been derived through in vitro study. This is a significant issue as the component parts of the immune system do not work in isolation and their interactions occur in distinct and specialized micro- and macro-anatomical locations that can only be assessed in the physiological context, in vivo. In this context, the availability of transgenic malaria parasites over the last 10 years has greatly enhanced our ability to understand and evaluate factors involved in host-parasite interactions in vivo. In this article, we review the current status of this area and speculate on what parasite transgenesis approaches will tell us about the development of Plasmodium-specific immune responses in the future.


Asunto(s)
Animales Modificados Genéticamente/inmunología , Interacciones Huésped-Parásitos/genética , Interacciones Huésped-Parásitos/inmunología , Plasmodium/genética , Plasmodium/inmunología , Animales , Humanos , Malaria/inmunología
5.
Inflamm Res ; 56(10): 391-401, 2007 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-18026695

RESUMEN

The induction of an adaptive immune response is an essential step in the generation of long-lasting, protective immunity to pathogens. Many studies over the last few decades have identified the cell populations involved in the generation of antigen-specific immunity and elucidated the role of many important molecules. However, because of the low precursor frequency of antigen-specific cells, the immune system must be highly dynamic, surveying most sites of the body. Recent studies have, therefore, begun to examine how the cells of the immune system interact in vivo during the induction of an immune response, identifying new and important roles for certain molecules and revealing how previously unrecognised alterations in cell-cell interactions can have significant implications for the resulting immune response. Here we review some of these recent studies that provide a valuable insight into the mechanisms involved in the induction of immunity.


Asunto(s)
Linfocitos/fisiología , Tejido Linfoide/inmunología , Animales , Presentación de Antígeno , Células Presentadoras de Antígenos/fisiología , Comunicación Celular , Movimiento Celular , Humanos , Mediciones Luminiscentes , Ganglios Linfáticos/inmunología , Activación de Linfocitos , Imagen por Resonancia Magnética , Microscopía , Transducción de Señal , Bazo/inmunología
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA
...