BACKGROUND: Corneal allograft survival dramatically decreases in hosts with inflamed or vascularized recipient beds. We have previously shown that in rejected corneal allografts regulatory T cells (Treg) demonstrate diminished Foxp3 expression and immunoregulatory function. Treatment with low doses of IL-2 selectively expands Treg and has been proposed for the treatment of autoimmune diseases. In this study, we investigated the effect of low-dose IL-2 administration on Treg function and corneal allograft survival. METHODS: Allogeneic corneal transplantation was performed on inflamed host beds. Low-dose systemic IL-2 was administered starting 3 days before grafting until 6 weeks after transplantation. Frequencies of Treg and their immunosuppressive function and antigen specificity were assessed using flow cytometry, in vitro proliferation assays, and adoptive transfer experiments. Frequencies of effector T cells (Teff) and graft infiltrating immune cells were measured at 2 weeks posttransplantation. Long-term allograft survival was evaluated for up to 9 weeks using Kaplan-Meier survival analysis. RESULTS: Treatment with low-dose IL-2 significantly increased frequencies of CD4CD25Foxp3 Treg and their immunosuppressive function. It also suppressed alloimmune response as shown by the decreased CD4 IFNγ T cell frequencies and graft infiltration of CD45 and CD4 cells. Clinical evaluation of the grafts showed significant improvement in long-term corneal allograft survival in the IL-2 treated group compared with controls. CONCLUSIONS: Our study is the first to report that treatment with low-dose IL-2 increases survival of corneal allografts. We propose that IL-2-mediated Treg expansion can be an effective tool to prevent alloimmunity and to improve long-term allograft survival in transplantation.
BACKGROUND: Corneal allograft survival dramatically decreases in hosts with inflamed or vascularized recipient beds. We have previously shown that in rejected corneal allografts regulatory T cells (Treg) demonstrate diminished Foxp3 expression and immunoregulatory function. Treatment with low doses of IL-2 selectively expands Treg and has been proposed for the treatment of autoimmune diseases. In this study, we investigated the effect of low-dose IL-2 administration on Treg function and corneal allograft survival. METHODS: Allogeneic corneal transplantation was performed on inflamed host beds. Low-dose systemic IL-2 was administered starting 3 days before grafting until 6 weeks after transplantation. Frequencies of Treg and their immunosuppressive function and antigen specificity were assessed using flow cytometry, in vitro proliferation assays, and adoptive transfer experiments. Frequencies of effector T cells (Teff) and graft infiltrating immune cells were measured at 2 weeks posttransplantation. Long-term allograft survival was evaluated for up to 9 weeks using Kaplan-Meier survival analysis. RESULTS: Treatment with low-dose IL-2 significantly increased frequencies of CD4CD25Foxp3 Treg and their immunosuppressive function. It also suppressed alloimmune response as shown by the decreased CD4 IFNγ T cell frequencies and graft infiltration of CD45 and CD4 cells. Clinical evaluation of the grafts showed significant improvement in long-term corneal allograft survival in the IL-2 treated group compared with controls. CONCLUSIONS: Our study is the first to report that treatment with low-dose IL-2 increases survival of corneal allografts. We propose that IL-2-mediated Treg expansion can be an effective tool to prevent alloimmunity and to improve long-term allograft survival in transplantation.
Authors: C B Pilon; S Petillon; S Naserian; G H Martin; C Badoual; P Lang; D Azoulay; E Piaggio; P Grimbert; J L Cohen Journal: Am J Transplant Date: 2014-11-13 Impact factor: 8.086
Authors: Lauren W Collison; Creg J Workman; Timothy T Kuo; Kelli Boyd; Yao Wang; Kate M Vignali; Richard Cross; David Sehy; Richard S Blumberg; Dario A A Vignali Journal: Nature Date: 2007-11-22 Impact factor: 49.962
Authors: S A Rosenberg; J C Yang; S L Topalian; D J Schwartzentruber; J S Weber; D R Parkinson; C A Seipp; J H Einhorn; D E White Journal: JAMA Date: 1994 Mar 23-30 Impact factor: 56.272
Authors: Casey O Lightbourn; Dietlinde Wolf; Sabrina N Copsel; Ying Wang; Brent J Pfeiffer; Henry Barreras; Cameron S Bader; Krishna V Komanduri; Victor L Perez; Robert B Levy Journal: Front Immunol Date: 2021-03-02 Impact factor: 7.561
Authors: Lokendrakumar C Bengani; Hidenaga Kobashi; Amy E Ross; Hualei Zhai; Borja Salvador-Culla; Rekha Tulsan; Paraskevi E Kolovou; Sharad K Mittal; Sunil K Chauhan; Daniel S Kohane; Joseph B Ciolino Journal: Acta Biomater Date: 2020-08-16 Impact factor: 8.947