RRC ID 43655
Author Lian G, Arimochi H, Kitamura A, Nishida J, Li S, Kishihara K, Maekawa Y, Yasutomo K.
Title Manipulation of CD98 resolves type 1 diabetes in nonobese diabetic mice.
Journal J Immunol
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.
Volume 188(5)
Pages 2227-34
Published 2012-3-1
DOI 10.4049/jimmunol.1102586
PII jimmunol.1102586
PMID 22291182
MeSH Animals Antibodies, Monoclonal / administration & dosage Antibodies, Monoclonal / therapeutic use CD4-Positive T-Lymphocytes / immunology CD4-Positive T-Lymphocytes / metabolism CD4-Positive T-Lymphocytes / pathology CD8-Positive T-Lymphocytes / immunology CD8-Positive T-Lymphocytes / metabolism CD8-Positive T-Lymphocytes / pathology Cyclophosphamide / administration & dosage Diabetes Mellitus, Type 1 / chemically induced Diabetes Mellitus, Type 1 / immunology* Diabetes Mellitus, Type 1 / prevention & control* Female Fusion Regulatory Protein 1, Heavy Chain / genetics Fusion Regulatory Protein 1, Heavy Chain / immunology Fusion Regulatory Protein 1, Heavy Chain / physiology* Growth Inhibitors / genetics Growth Inhibitors / metabolism Growth Inhibitors / physiology Mice Mice, Inbred BALB C Mice, Inbred C57BL Mice, Inbred NOD Mice, SCID Mice, Transgenic Rats Rats, Wistar
IF 4.718
Times Cited 5
Human and Animal Cells