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 (Tregs) demonstrate diminished Foxp3 expression and immunoregulatory function. Treatment with low doses of IL-2 selectively expands Tregs 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 three days before grafting until six weeks after transplantation. Frequencies of Tregs as well as 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 post-transplantation. 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 CD4+CD25+Foxp3+ Tregs 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 to 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.
The MCA comprise a network of branched interlinked elliptical loops supporting circumferential blood flow in the corneal periphery. There was no definable change in vascular pattern extending into the limbal region.
PURPOSE.To investigate the rate of recurrent bacterial keratitis, associated bacteria, and surgical intervention. METHODS.Patients with suspected bacterial keratitis were identified from microbiological requests over a 16-year period between 1995 and 2010. Recurrences and number of surgical interventions were analyzed according to bacterial type. RESULTS.A total of 2418 patients were included, of whom 2124 (87.84%) had only one episode of keratitis, 294 (12.15%) at least two, 88 (3.63%) at least three, 40 (1.65%) at least four, and 22 (0.91%) five or more episodes. The bacterial isolation rate was 35.74% (SD 9.41%), increasing to 56.01% in patients with two or more episodes. There was an increase in the isolation of Staphylococcus aureus with increasing number of episodes (P ¼ 0.008), and S. aureus occurred more commonly in patients with recurrent disease due to the same bacterial group (P ¼ 0.04). Patients whose recurrent keratitis was associated with S. aureus had a higher rate of requiring subsequent corneal transplantation (7 of 10) compared to those with Enterobacteriaceae (2 of 7), Pseudomonas aeruginosa (2 of 4), streptococci (2 of 5), or coagulase-negative staphylococci (none of 8) (P ¼ 0.02).CONCLUSIONS. S. aureus is particularly associated with recurrent keratitis. Identification and treatment of the possible source of the infection may be necessary to reduce the risk of recurrent disease. The potential for the autocthonous S. aureus colonizing the nasopharynx or conjunctiva or lid margin to be a reservoir for recurrent keratitis suggests that decolonization of S. aureus could be considered as a potential intervention in those patients with recurrent disease.
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