RESUMEN

Dendritic cells are rare haematopoietic cells that reside in a number of organs and tissues. By capturing, processing and presenting antigens to T cells, dendritic cells are essential for immune surveillance and the regulation of specific immunity. Several members of the tumour necrosis factor receptor (TNFR) superfamily are integral to the regulation of the immune response. These structurally related proteins modulate cellular functions ranging from proliferation and differentiation to inflammation and cell survival or deaths. The functional activity of dendritic cells is greatly increased by signalling through the TNFR family member CD40. Here we report the characterization of RANK (for receptor activator of NF-kappaB), a new member of the TNFR family derived from dendritic cells, and the isolation of a RANK ligand (RANKL) by direct expression screening. RANKL augments the ability of dendritic cells to stimulate naive T-cell proliferation in a mixed lymphocyte reaction, and increases the survival of RANK+ T cells generated with interleukin-4 and transforming growth factor (TGF)-beta. Thus RANK and RANKL seem to be important regulators of interactions between T cells and dendritic cells.

Asunto(s)

Proteínas Portadoras , Células Dendríticas/inmunología , Receptores del Factor de Necrosis Tumoral/inmunología , Linfocitos T/inmunología , Secuencia de Aminoácidos , Animales , Ligando de CD40 , Línea Celular , Células Cultivadas , Mapeo Cromosómico , Cromosomas Humanos Par 13 , Cromosomas Humanos Par 18 , Humanos , Ligandos , Glicoproteínas de Membrana/metabolismo , Proteínas de la Membrana/metabolismo , Ratones , Datos de Secuencia Molecular , Ligando RANK , Receptor Activador del Factor Nuclear kappa-B , Receptores del Factor de Necrosis Tumoral/análisis , Receptores del Factor de Necrosis Tumoral/genética , Homología de Secuencia de Aminoácido , Transfección