| RRC ID |
43655
|
| 著者 |
Lian G, Arimochi H, Kitamura A, Nishida J, Li S, Kishihara K, Maekawa Y, Yasutomo K.
|
| タイトル |
Manipulation of CD98 resolves type 1 diabetes in nonobese diabetic mice.
|
| ジャーナル |
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.
|
| 巻・号 |
188(5)
|
| ページ |
2227-34
|
| 公開日 |
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 |
4.886
|
| 引用数 |
5
|
|
WOS 分野
|
IMMUNOLOGY
|
| リソース情報 |
| ヒト・動物細胞 |
|
