title: Induction of tolerance in murine autoimmune diabetes by transient blockade of leukocyte function-associated antigen-1/intercellular adhesion molecule-1 pathway.
abstract: The present study demonstrated that a short-term administration of mAbs against leukocyte function-associated antigen-1 (LFA-1) and intercellular adhesion molecule-1 (ICAM-1) at critical periods resulted in complete protection of autoimmune diabetes in non-obese diabetic (NOD) mice. When these mAbs were administered for only 6 days at 2 wk of age, neither diabetes nor insulitis was observed at 30 wk of age. It appears that the tolerance against beta cell Ag(s) was induced by this transient blockade of the LFA-1/ICAM-1 pathway. Protective suppressor activity was not enough to prevent diabetes because co-transfer of splenocytes from female NOD mice, which had received these mAbs at 2 wk of age, resulted in only a short delay of the diabetic onset caused by adoptive transfer of splenocytes from acutely diabetic NOD mice. Transfer of these splenocytes to young NOD mice could not also abrogate the spontaneous diabetes and insulitis. Furthermore, cyclophosphamide treatment could not abrogate the protection. When splenocytes from the treated NOD mice were transferred to NOD-SCID mice, none of the recipient mice developed significant insulitis and subsequent overt diabetes, suggesting the absence or the inactivation of diabetogenic effector T cells. However, splenic T cells from the insulitis-free NOD mice that had received the mAb treatment preserved proliferative responses to both islet cells and 65-kDa glutamic acid decarboxylase (GAD65) in vitro. These results suggest that a unique peripheral tolerance was induced by the transient blockade of the LFA-1/ICAM-1 pathway in an early age of NOD mice.
authors.affiliation: Second Department of Internal Medicine, Kobe University School of Medicine, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Moriyama
authors.forename: K
authors.initials: K
authors.lastname: Yokono
authors.forename: K
authors.initials: K
authors.lastname: Amano
authors.forename: M
authors.initials: M
authors.lastname: Nagata
authors.forename: Y
authors.initials: Y
authors.lastname: Hasegawa
authors.forename: N
authors.initials: N
authors.lastname: Okamoto
authors.forename: K
authors.initials: K
authors.lastname: Tsukamoto
authors.forename: M
authors.initials: M
authors.lastname: Miki
authors.forename: R
authors.initials: R
authors.lastname: Yoneda
authors.forename: N
authors.initials: N
authors.lastname: Yagi
authors.forename: Y
authors.initials: Y
authors.lastname: Tominaga
authors.forename: H
authors.initials: H
authors.lastname: Kikutani
authors.forename: K
authors.initials: K
authors.lastname: Hioki
authors.forename: K
authors.initials: K
authors.lastname: Okumura
authors.forename: H
authors.initials: H
authors.lastname: Yagita
authors.forename: M
authors.initials: M
authors.lastname: Kasuga
mesh_terms: D019264:Adoptive Transfer; D000367:Age Factors; D000818:Animals; D019138:Antibodies, Blocking / Q000494:pharmacology; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D015551:Autoimmunity; D003520:Cyclophosphamide / Q000494:pharmacology; D003922:Diabetes Mellitus, Type 1 / Q000209:etiology / Q000276:immunology* / Q000517:prevention & control; D005260:Female; D005968:Glutamate Decarboxylase / Q000276:immunology; D007108:Immune Tolerance; D007165:Immunosuppression Therapy; D007166:Immunosuppressive Agents / Q000494:pharmacology; D018799:Intercellular Adhesion Molecule-1 / Q000276:immunology*; D007515:Islets of Langerhans / Q000276:immunology; D008213:Lymphocyte Activation; D016169:Lymphocyte Function-Associated Antigen-1 / Q000276:immunology*; D008297:Male; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D013154:Spleen / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D019138:Antibodies, Blocking; D000911:Antibodies, Monoclonal; D007166:Immunosuppressive Agents; D016169:Lymphocyte Function-Associated Antigen-1; D018799:Intercellular Adhesion Molecule-1; D003520:Cyclophosphamide; D005968:Glutamate Decarboxylase