Local and Systemic Immunologic Profiles Differentiate Accepted and Rejected Islet Grafts in a Rat Anterior Chamber Model.

Abstract

The anterior chamber of the eye (ACE) provides a minimally invasive, immune-privileged site for pancreatic islet engraftment. However, loss of immune privilege during revascularization can trigger inflammation and graft rejection. In this study, we compared ocular and systemic immunologic responses associated with accepted and rejected islet allografts in the ACE. Lewis rat recipients underwent ACE allogeneic islet transplantation without immunosuppressive agents. Ocular grafts and spleens were examined by histology and immunofluorescence for effector and regulatory T-cell (Treg) populations. Systemic and local cytokines were also quantified and compared between accepted and rejected groups. Graft function (glycemic control) was monitored for 30 days, and diabetic retinopathy development was evaluated histologically. We found glycemic control was lost by 3 weeks in allo-rejected rats, whereas allo-accepted rats maintained euglycemia throughout this period. Rats with accepted grafts demonstrated reduced local immune cell infiltration in ACE locally and increased splenic Foxp3⁺ Treg systemically. In contrast, rats with rejected grafts exhibited extensive T-cell infiltration in both the eye and spleen, decreased splenic Treg populations, elevated local and systemic inflammatory cytokines, and worsened glucose control and diabetic retinal development. Taken together, these results suggest that integrated profiling of local and systemic immunologic signatures effectively distinguishes accepted from rejected ACE islet allografts, and early postoperative monitoring of interleukin 6 (IL-6), interferon gamma (IFN-γ), and IL-10 within the first 3 weeks could facilitate timely, targeted immunosuppression therapy.