The Novel Costimulatory Programmed Death Ligand 1/B7.1 Pathway Is Functional in Inhibiting Alloimmune Responses In Vivo
- 1 August 2011
- journal article
- Published by The American Association of Immunologists in The Journal of Immunology
- Vol. 187 (3), 1113-1119
- https://doi.org/10.4049/jimmunol.1100056
Abstract
The programmed death ligand 1 (PDL1)/programmed death 1 (PD1) costimulatory pathway plays an important role in the inhibition of alloimmune responses as well as in the induction and maintenance of peripheral tolerance. It has been demonstrated recently that PDL1 also can bind B7.1 to inhibit T cell responses in vitro. Using the bm12 into B6 heart transplant model, we investigated the functional significance of this interaction in alloimmune responses in vivo. PD1 blockade unlike PDL1 blockade failed to accelerate bm12 allograft rejection, suggesting a role for an additional binding partner for PDL1 other than PD1 in transplant rejection. PDL1 blockade was able to accelerate allograft rejection in B7.2-deficient recipients but not B7.1-deficient recipients, indicating that PDL1 interaction with B7.1 was important in inhibiting rejection. Administration of the novel 2H11 anti-PDL1 mAb, which only blocks the PDL1–B7.1 interaction, aggravated chronic injury of bm12 allografts in B6 recipients. Aggravated chronic injury was associated with an increased frequency of alloreactive IFN-γ–, IL-4–, and IL-6–producing splenocytes and a decreased percentage of regulatory T cells in the recipients. Using an in vitro cell culture assay, blockade of the interaction of PDL1 on dendritic cells with B7.1 on T cells increased IFN-γ production from alloreactive CD4+ T cells, whereas blockade of dendritic cell B7.1 interaction with T cell PDL1 did not. These data indicate that PDL1 interaction with B7.1 plays an important role in the inhibition of alloimmune responses in vivo and suggests a dominant direction for PDL1 and B7.1 interaction.Keywords
This publication has 31 references indexed in Scilit:
- B7-H1/CD80 interaction is required for the induction and maintenance of peripheral T-cell toleranceBlood, 2010
- PD-L1 regulates the development, maintenance, and function of induced regulatory T cellsThe Journal of Experimental Medicine, 2009
- Down‐modulation of programmed death 1 alters regulatory T cells and promotes experimental autoimmune encephalomyelitisJournal of Neuroscience Research, 2009
- A novel role of CD4 Th17 cells in mediating cardiac allograft rejection and vasculopathyThe Journal of Experimental Medicine, 2008
- Control of peripheral T‐cell tolerance and autoimmunity via the CTLA‐4 and PD‐1 pathwaysImmunological Reviews, 2008
- PD-1 and Its Ligands in Tolerance and ImmunityAnnual Review of Immunology, 2008
- Critical Role of Donor Tissue Expression of Programmed Death Ligand-1 in Regulating Cardiac Allograft Rejection and VasculopathyCirculation, 2008
- Programmed Death-1 Ligand 1 Interacts Specifically with the B7-1 Costimulatory Molecule to Inhibit T Cell ResponsesImmunity, 2007
- Estrogen-mediated immunomodulation involves reduced activation of effector T cells, potentiation of treg cells, and enhanced expression of the PD-1 costimulatory pathwayJournal of Neuroscience Research, 2006
- Tissue expression of PD-L1 mediates peripheral T cell toleranceThe Journal of Experimental Medicine, 2006