The role of the ICOS-B7h T cell costimulatory pathway in transplantation immunity
AUTOR(ES)
Harada, Hiroshi
FONTE
American Society for Clinical Investigation
RESUMO
Inducible costimulatory molecule (ICOS) plays a pivotal role in T cell activation and Th1/Th2 differentiation. ICOS blockade has disparate effects on immune responses depending on the timing of blockade. Its role in transplantation immunity, however, remains incompletely defined. We used a vascularized mouse cardiac allograft model to explore the role of ICOS signaling at different time points after transplantation, targeting immune initiation (early blockade) or the immune effector phase (delayed blockade). In major histocompatibility–mismatched recipients, ICOS blockade prolonged allograft survival using both protocols but did so more effectively in the delayed-treatment group. By contrast, in minor histocompatibility–mismatched recipients, early blockade accelerated rejection and delayed blockade prolonged graft survival. Alloreactive CD4+ T cell expansion and alloantibody production were suppressed in both treatment groups, whereas only delayed blockade resulted in suppression of effector CD8+ T cell generation. After delayed ICOS blockade, there was a diminished frequency of allospecific IL-10–producing cells and an increased frequency of both IFN-γ– and IL-4–producing cells. The beneficial effects of ICOS blockade in regulating allograft rejection were seen in the absence of CD28 costimulation but required CD8+ cells, cytotoxic T lymphocyte antigen-4, and an intact signal transducer and activator of transcription–6 pathway. These data define the complex functions of the ICOS-B7h pathway in regulating alloimmune responses in vivo.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=164288Documentos Relacionados
- Disruption of the ICOS-B7RP-1 Costimulatory Pathway Leads to Enhanced Hepatic Immunopathology and Increased Gamma Interferon Production by CD4 T Cells in Murine Schistosomiasis
- The role of the B7 costimulatory pathway in experimental cold ischemia/reperfusion injury.
- Modulation of Murine Lyme Borreliosis by Interruption of the B7/CD28 T-Cell Costimulatory Pathway
- Bacterial Pathogens Induce Abscess Formation by CD4+ T-Cell Activation via the CD28–B7-2 Costimulatory Pathway
- Role of B7 Costimulatory Molecules in Immune Responses and T-Helper Cell Differentiation in Response to Recombinant HagB from Porphyromonas gingivalis