| RRC ID |
12160
|
| 著者 |
Setoguchi K, Misaki Y, Araki Y, Fujio K, Kawahata K, Kitamura T, Yamamoto K.
|
| タイトル |
Antigen-specific T cells transduced with IL-10 ameliorate experimentally induced arthritis without impairing the systemic immune response to the antigen.
|
| ジャーナル |
J Immunol
|
| Abstract |
For the treatment of rheumatoid arthritis, efficient drug delivery methods to the inflamed joints need to be developed. Because T cells expressing an appropriate autoantigen-specific receptor can migrate to inflamed lesions, it has been reasoned that they can be employed to deliver therapeutic agents. To examine the ability and efficiency of such T cells as a vehicle, we employed an experimentally induced model of arthritis. Splenic T cells from DO11.10 TCR transgenic mice specific for OVA were transduced with murine IL-10. Adoptive transfer of the IL-10-transduced DO11.10 splenocytes ameliorated OVA-induced arthritis despite the presence of around 95% nontransduced cells. Using green fluorescent protein as a marker for selection, the number of transferred cells needed to ameliorate the disease was able to be reduced to 10(4). Preferential accumulation of the transferred T cells was observed in the inflamed joint, and the improvement in the disease was not accompanied by impairment of the systemic immune response to the Ag, suggesting that the transferred T cells exert their anti-inflammatory task locally, mainly in the joints where the Ag exists. In addition, IL-10-transduced DO11.10 T cells ameliorated methylated BSA-induced arthritis when the arthritic joint was coinjected with OVA in addition to methylated BSA. These results suggest that T cells specific for a joint-specific Ag would be useful as a therapeutic vehicle in rheumatoid arthritis for which the arthritic autoantigen is still unknown.
|
| 巻・号 |
165(10)
|
| ページ |
5980-6
|
| 公開日 |
2000-11-15
|
| DOI |
10.4049/jimmunol.165.10.5980
|
| PMID |
11067961
|
| MeSH |
Animals
Antigens / administration & dosage
Antigens / immunology*
Antigens / pharmacology
Arthritis, Experimental / genetics
Arthritis, Experimental / immunology*
Arthritis, Experimental / pathology
Arthritis, Experimental / therapy*
CD4-Positive T-Lymphocytes / immunology
CD4-Positive T-Lymphocytes / metabolism
CD4-Positive T-Lymphocytes / transplantation*
Cell Movement / genetics
Cell Movement / immunology
Dose-Response Relationship, Immunologic
Epitopes, T-Lymphocyte / genetics*
Female
Genetic Vectors / immunology
Genetic Vectors / metabolism
Green Fluorescent Proteins
Immunity, Cellular / genetics
Injections, Intra-Articular
Interleukin-10 / genetics*
Joints / immunology
Joints / pathology
Luminescent Proteins / biosynthesis
Lymphocyte Activation / genetics
Lymphocyte Count
Lymphocyte Transfusion
Mice
Mice, Inbred BALB C
Mice, Transgenic
Ovalbumin / administration & dosage
Ovalbumin / immunology*
Ovalbumin / pharmacology
Retroviridae / genetics
Retroviridae / immunology
Serum Albumin, Bovine / immunology
Severity of Illness Index
Spleen / cytology
Spleen / immunology
Spleen / metabolism
Spleen / transplantation
Transduction, Genetic*
|
| IF |
4.886
|
| 引用数 |
35
|
|
WOS 分野
|
IMMUNOLOGY
|
| リソース情報 |
| 遺伝子材料 |
pMFGmIL10 (RDB1446) |
