Type I diabetes (T1D) results from T cell destruction of pancreatic beta-cells that leads to insulin ablation. Autoimmune attacks on beta cells occur, due to defective immune tolerance and escape of autoreactive T cells from regulation. There is no cure available for T1D, and patients rely on exogenous insulin to regulate their blood glucose, which does not prevent life-threatening complications. Transgenic Ins2-CCL21 non-obese diabetic mice, secreting immunomodulatory chemokine CCL21 from their beta-cells, are protected from T1D, while transplantation of Ins2-CCL21islets in non-transgenic mice delayed T1D onset. Local and systemic protection from T1D was associated with formation of tolerogenic stromal cell networks near the CCL21-secreting islets. To recapitulate transgenic islets and reinstate T1D tolerance, we developed hydrogels delivering CCL21 and beta-cell antigens (BDC2.5). CCL21 and BDC2.5 were linked to polyethylene glycol (PEG) hydrogels and implanted under the kidney capsule of prediabetic NOD mice that received injection of BDC2.5.CD45.2 splenocytes. We quantified different immune cell populations in the pancreata through immunofluorescence. There were slightly more regulatory T cells in the infiltrates of CCL21 + BDC2.5 gels recipients than control gels. Additionally, we quantified islet size by measuring Ferret's diameter in ImageJ. There was no significant difference in islet size between control and CCL21 + BDC2.5 gel recipients, which suggested there was no significant difference in islet damage. These results show the potential for increasing regulation of autoreactive T cells by inducing tolerance with our CCL21 + BDC2.5 delivery platform.
