title: Manipulation of CD98 resolves type 1 diabetes in nonobese diabetic mice.
abstract: The interplay of CD4(+) and CD8(+) T cells targeting autoantigens is responsible for the progression of a number of autoimmune diseases, including type 1 diabetes mellitus (T1D). Understanding the molecular mechanisms that regulate T cell activation is crucial for designing effective therapies for autoimmune diseases. We probed a panel of Abs with T cell-modulating activity and identified a mAb specific for the H chain of CD98 (CD98hc) that was able to suppress T cell proliferation. The anti-CD98hc mAb also inhibited Ag-specific proliferation and the acquisition of effector function by CD4(+) and CD8(+) T cells in vitro and in vivo. Injection of the anti-CD98hc mAb completely prevented the onset of cyclophosphamide-induced diabetes in NOD mice. Treatment of diabetic NOD mice with anti-CD98hc reversed the diabetic state to normal levels, coincident with decreased proliferation of CD4(+) T cells. Furthermore, treatment of diabetic NOD mice with CD98hc small interfering RNA resolved T1D. These data indicate that strategies targeting CD98hc might have clinical application for treating T1D and other T cell-mediated autoimmune diseases.
authors.affiliation: Department of Immunology and Parasitology, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima 770-8503, Japan.
authors.forename: Gaojian
authors.initials: G
authors.lastname: Lian
authors.forename: Hideki
authors.initials: H
authors.lastname: Arimochi
authors.forename: Akiko
authors.initials: A
authors.lastname: Kitamura
authors.forename: Jun
authors.initials: J
authors.lastname: Nishida
authors.forename: Shigen
authors.initials: S
authors.lastname: Li
authors.forename: Kenji
authors.initials: K
authors.lastname: Kishihara
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Maekawa
authors.forename: Koji
authors.initials: K
authors.lastname: Yasutomo
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000627:therapeutic use; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D003520:Cyclophosphamide / Q000008:administration & dosage; D003922:Diabetes Mellitus, Type 1 / Q000139:chemically induced / Q000276:immunology* / Q000517:prevention & control*; D005260:Female; D027282:Fusion Regulatory Protein 1, Heavy Chain / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D006131:Growth Inhibitors / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D008822:Mice, Transgenic; D051381:Rats; D017208:Rats, Wistar
chemical_list: D000911:Antibodies, Monoclonal; D027282:Fusion Regulatory Protein 1, Heavy Chain; D006131:Growth Inhibitors; C420942:ILAT protein, rat; C523212:Slc3A2 protein, mouse; D003520:Cyclophosphamide