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Role of Lentivirus‐Mediated Overexpression of Programmed Death‐Ligand 1 on Corneal Allograft Survival
Author(s) -
Nosov M.,
Wilk M.,
Morcos M.,
Cregg M.,
O’Flynn L.,
Treacy O.,
Ritter T.
Publication year - 2012
Publication title -
american journal of transplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.89
H-Index - 188
eISSN - 1600-6143
pISSN - 1600-6135
DOI - 10.1111/j.1600-6143.2011.03948.x
Subject(s) - medicine , corneal transplantation , cd8 , proinflammatory cytokine , in vivo , cornea , viral vector , ex vivo , green fluorescent protein , microbiology and biotechnology , immunology , andrology , cancer research , immune system , biology , ophthalmology , gene , inflammation , biochemistry , recombinant dna
To investigate the role of lentivirus‐mediated overexpression of programmed death‐ligand 1 (PD‐L1) on rat corneal allograft survival. A fully allogeneic rat cornea transplant model was used for in vivo studies. Lentiviral (LV) vectors are efficient tools for ex vivo genetic modification of cultured corneas. LV vector encoding for PD‐L1 (LV.PD‐L1) and LV vector encoding for eGFP (LV.eGFP, as control) were constructed and tested. PD‐L1 or eGFP expression was increased on corneal cells upon LV.PD‐L1 and LV.eGFP transduction, respectively. Both allogeneic controls and allogeneic LV.eGFP transduced corneas were uniformly rejected (MST: 13.8 ± 1.7 days and 12.3 ± 1.9 days, respectively). In contrast, allogeneic LV.PD‐L1 transduced corneas showed a high percentage (83%) of graft survival (MST > 30 days, n = 5, 15 days, n = 1). Graft opacity of PD‐L1 transduced corneas was present but was significantly reduced compared to control or eGFP expressing corneas. Flow cytometric analysis revealed that percentages of CD3 + CD8 + CD161 + and CD3 + CD8 + CD161 – lymphocytes were decreased in animals receiving LV.PD‐L1 transduced corneas compared to animals grafted with LV.eGFP transduced corneas. Moreover, reduced expression of proinflammatory cytokines (IFN‐γ and IL‐6) in PD‐L1 transduced corneas compared to allogeneic controls was also observed. Local PD‐L1 gene transfer in cultured corneas is a promising approach for the prolongation of corneal allograft survival and attenuation of graft rejection.