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Active tolerance induction and involvement of CD1d‐restricted NKT cells in anti‐CD3 F(ab¡¯)2 treatment reversed new onset diabetes in NOD mice
Author(s) -
Han gencheng,
Chen Guojiang,
Li Yan,
Shen Beifen
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.2_supplement.458
Subject(s) - cd1d , nod , nod mice , natural killer t cell , immunology , type 1 diabetes , immune system , antibody , monoclonal antibody , diabetes mellitus , cd3 , medicine , t cell , biology , endocrinology , cd8
The application of anti‐CD3 F(ab’) 2 monoclonal antibodies recently has been expanded to treat established autoimmune diseases including type 1 diabetes. However, the underling mechanisms remain largely unclear. Here, we report that short‐phase administration of anti‐CD3 F(ab’) 2 antibodies efficiently converted new‐onset diabetic nonobese diabetic mice into normoglycemia and re‐established pancreatic β‐cell specific tolerance, this therapeutic effect lasting over 40 weeks. The understanding of involving mechanism revealed the generation of a population of immunoregulatory CD1d‐restricted natural killer T (NKT) cells, which was marked by enhanced Th2 response and secreting more IL‐10. In vivo neutralization of IL‐4 and/or IL‐10 bioactivity abrogated this anti‐CD3‐mediated effect. Importantly, when cotransfer of remitting mice derived NKT cells into NOD‐severe combined immunodeficient (NOD.scid) mice with diabetogenic cells, these NKT cells were sufficient to delay or prevent the onset of diabetes. These data suggested that CD1d‐restricted NKT cells might play a critical role in anti‐CD3 antibody induced diabetes remission and immune tolerance restoration.