title: Anti-CD3/Anti-CXCL10 Antibody Combination Therapy Induces a Persistent Remission of Type 1 Diabetes in Two Mouse Models.
abstract: 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.
authors: Pharmazentrum Frankfurt/ZAFES, Goethe University Hospital Frankfurt, Frankfurt am Main, Germany.
authors: Stanley
authors: S
authors: Lasch
authors: Pharmazentrum Frankfurt/ZAFES, Goethe University Hospital Frankfurt, Frankfurt am Main, Germany.
authors: Peter
authors: P
authors: Müller
authors: Pharmazentrum Frankfurt/ZAFES, Goethe University Hospital Frankfurt, Frankfurt am Main, Germany.
authors: Monika
authors: M
authors: Bayer
authors: Pharmazentrum Frankfurt/ZAFES, Goethe University Hospital Frankfurt, Frankfurt am Main, Germany.
authors: Josef M
authors: JM
authors: Pfeilschifter
authors: Massachusetts General Hospital, Harvard Medical School, Boston, MA.
authors: Andrew D
authors: AD
authors: Luster
authors: Pharmazentrum Frankfurt/ZAFES, Goethe University Hospital Frankfurt, Frankfurt am Main, Germany.
authors: Edith
authors: E
authors: Hintermann
authors: Pharmazentrum Frankfurt/ZAFES, Goethe University Hospital Frankfurt, Frankfurt am Main, Germany christen@med.uni-frankfurt.de.
authors: Urs
authors: http://orcid.org/0000-0003-4165-7976
authors: U
authors: Christen
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000627:therapeutic use*; D015551:Autoimmunity / Q000187:drug effects*; D017252:CD3 Complex / Q000737:chemistry* / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D054357:Chemokine CXCL10 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D003433:Crosses, Genetic; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination; D005260:Female; D007004:Hypoglycemic Agents / Q000009:adverse effects / Q000627:therapeutic use; D007515:Islets of Langerhans / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008213:Lymphocyte Activation / Q000187:drug effects; D008810:Mice, Inbred C57BL; D016688:Mice, Inbred NOD; D008822:Mice, Transgenic; D058990:Molecular Targeted Therapy; D012074:Remission Induction; D013154:Spleen / Q000187:drug effects / Q000473:pathology; D016019:Survival Analysis
chemical_list: D000911:Antibodies, Monoclonal; D017252:CD3 Complex; D054357:Chemokine CXCL10; C485433:Cxcl10 protein, mouse; D007004:Hypoglycemic Agents