Notch ligation by Delta1 inhibits peripheral immune responses to transplantation antigens by a CD8+ cell–dependent mechanism
AUTOR(ES)
Wong, Kenneth K.
FONTE
American Society for Clinical Investigation
RESUMO
Notch signaling plays a fundamental role in determining the outcome of differentiation processes in many tissues. Notch signaling has been implicated in T versus B cell lineage commitment, thymic differentiation, and bone marrow hematopoietic precursor renewal and differentiation. Notch receptors and their ligands are also expressed on the surface of mature lymphocytes and APCs, but the effects of Notch signaling in the peripheral immune system remain poorly defined. The aim of the studies reported here was to investigate the effects of signaling through the Notch receptor using a ligand of the Delta-like family. We show that Notch ligation in the mature immune system markedly decreases responses to transplantation antigens. Constitutive expression of Delta-like 1 on alloantigen-bearing cells renders them nonimmunogenic and able to induce specific unresponsiveness to a challenge with the same alloantigen, even in the form of a cardiac allograft. These effects could be reversed by depletion of CD8+ cells at the time of transplantation. Ligation of Notch on splenic CD8+ cells results in a dramatic decrease in IFN-γ with a concomitant enhancement of IL-10 production, suggesting that Notch signaling can alter the differentiation potential of CD8+ cells. These data implicate Notch signaling in regulation of peripheral immunity and suggest a novel approach for manipulating deleterious immune responses.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=281641Documentos Relacionados
- Induction of CD4+ T cell-dependent CD8+ type 1 responses in humans by a malaria DNA vaccine
- In vitro immune responses to a T cell-dependent antigen by cultures of disassociated murine Peyer's patch
- Evidence that resolution of rotavirus infection in mice is due to both CD4 and CD8 cell-dependent activities.
- CTLA4Ig inhibits T cell–dependent B-cell maturation in murine systemic lupus erythematosus
- An endothelial cell-dependent pathway of coagulation.