RESUMO
Regulatory mechanisms exist in the immune system to limit the induction of pathogenic responses to antigens encountered within the respiratory tract. The development of allergic disease is thought to arise as a result of the breakdown in these regulatory processes. In this review we examine the nature of immune responses generated to inhaled protein antigens and the mechanisms used to establish tolerance to inhaled antigens.
Assuntos
Antígenos/imunologia , Tolerância Imunológica/imunologia , Hipersensibilidade Respiratória/imunologia , Humanos , Subpopulações de Linfócitos T/imunologiaRESUMO
Signals derived from antigen-presenting cells (APC) influence the functional differentiation of CD4(+) T cells. We report here that Serrate1 (Jagged1), a ligand for the Notch1 receptor, may contribute to the differentiation of peripheral CD4(+) T cells into either helper or regulatory cells. Our findings demonstrate that antigen presented by murine APC overexpressing human Serrate1 induces naive peripheral CD4(+) T cells to become regulatory cells. These cells can inhibit primary and secondary immune responses, and transfer antigen-specific tolerance to recipient mice. Our results show that Notch signalling may help explain 'linked' suppression in peripheral tolerance, whereby tolerance induced to one epitope encompasses all epitopes on that antigen during the course of an immune response.
Assuntos
Linfócitos T CD4-Positivos/imunologia , Tolerância Imunológica , Proteínas de Membrana/metabolismo , Transdução de Sinais , Animais , Células Apresentadoras de Antígenos/imunologia , Células Apresentadoras de Antígenos/metabolismo , Antígenos de Dermatophagoides , Proteínas de Ligação ao Cálcio , Células Cultivadas , Epitopos/imunologia , Feminino , Regulação da Expressão Gênica/imunologia , Glicoproteínas/imunologia , Humanos , Imunidade Celular , Imunização , Peptídeos e Proteínas de Sinalização Intercelular , Proteína Jagged-1 , Leucócitos Mononucleares/imunologia , Proteínas de Membrana/genética , Camundongos , Ovalbumina/imunologia , Ratos , Receptores Notch , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Proteínas Serrate-JaggedRESUMO
Immunological tolerance is defined as a state of specific non-responsiveness to a particular antigen induced by previous exposure to that same antigen. The mucosal surfaces comprise the upper and lower respiratory tracts, the gastrointestinal tract and the urogenitary tract, and are a major site of antigenic challenge. The immune system associated with the mucosa has the extraordinary potential to discriminate between antigens that are harmless (e.g. inhaled and dietary antigens) and those that are associated with pathogens. Normally soluble proteins delivered through the mucosal surfaces do not elicit a strong systemic immune response but instead induce a transient local immune response that is replaced by long-term peripheral unresponsiveness this is termed mucosal tolerance. The phenomenon of oral tolerance is well established and considerable attention has focussed on defining the underlying mechanisms. However, only comparatively recently was the induction of tolerance via the respiratory mucosa described, and it is this form of mucosal tolerance which forms the basis of this review.
