Anti-CD3 therapy of type 1 diabetes results in a temporary halt of its pathogenesis but does not constitute a permanent cure. One problem is the reinfiltration of islets of Langerhans with regenerated, autoaggressive lymphocytes. We aimed at blocking such a reentry by neutralizing the key chemokine CXCL10. Combination therapy of diabetic RIP-LCMV and NOD mice with anti-CD3 and anti-CXCL10 antibodies caused a substantial remission of diabetes and was superior to monotherapy with anti- CD3 or anti-CXCL10 alone. The combination therapy prevented islet-specific T cells from reentering the islets of Langerhans and thereby blocked the autodestructive process. In addition, the local immune balance in the pancreas was shifted toward a regulatory phenotype. A sequential temporal inactivation of T cells and blockade of T-cell migration might constitute a novel therapy for patients with type 1 diabetes.
CITATION STYLE
Lasch, S., Müller, P., Bayer, M., Pfeilschifter, J. M., Luster, A. D., Hintermann, E., & Christen, U. (2015). Anti-CD3/Anti-CXCL10 antibody combination therapy induces a persistent remission of type 1 diabetes in two mouse models. Diabetes, 64(12), 4198–4211. https://doi.org/10.2337/db15-0479
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