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L. Shen, Y. Jin, G. J. Freeman, A. H. Sharpe, R. Dana; The Role of Donor versus Recipient PD-L1 in Corneal Allograft Survival. Invest. Ophthalmol. Vis. Sci. 2007;48(13):188.
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The Programmed Death-1 (PD-1):PD-Ligand 1 (PD-L1) pathway plays an important role in down-regulating immune responses and maintaining peripheral tolerance. We previously demonstrated that PD-L1 is constitutively expressed on corneal epithelial cells and infiltrating bone marrow-derived cells. This study examines the role of PD-L1 expression within the donor tissue versus the recipient in regulating alloimmune responses.
To dissect the role of donor versus recipient PD-L1 in modulating alloimmune responses, we used PD-L1-/- C57BL/6 mice as either donors or recipients of fully (multiple MHC and minor H) mismatched BALB/c corneal grafts. Allograft survival was measured by Kaplan-Meier analysis. Induction of alloreactive T cells through the indirect sensitization pathway, the principal route of T cell sensitization in low-risk corneal transplantation mediated by recipient APC, was measured by the IFN-γ-ELISPOT assay.
When PD-L1-/- C57BL/6 mice were used as recipients of allogeneic BALB/c corneas, the graft rejection was enhanced compared to that seen in wild-type recipients (0% versus 21% survival, P = 0.028). Importantly, when the PD-L1-/- C57BL/6 corneal grafts were transplanted onto wild-type BALB/c recipients, PD-L1 deficient allografts were significantly more susceptible to rejection than wild-type allografts (20% versus 53% survival, P = 0.047). The frequency of IFN-γ-producing T cells activated via the indirect pathway was significantly higher in PD-L1-/- recipients, but not in mice harboring PD-L1-/- corneal allografts.
Corneal allograft survival relies not only on recipient PD-L1 expression, but also significantly on PD-L1 expression by graft cells. Recipient PD-L1 enhances allograft survival by suppressing the induction phase of alloreactive T cells, while donor tissue-expressed PD-L1 may exert its protective role by attenuating allospecific effectors.
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