| RRC ID |
4783
|
| 著者 |
Nakajima A, Seroogy CM, Sandora MR, Tarner IH, Costa GL, Taylor-Edwards C, Bachmann MH, Contag CH, Fathman CG.
|
| タイトル |
Antigen-specific T cell-mediated gene therapy in collagen-induced arthritis.
|
| ジャーナル |
J Clin Invest
|
| Abstract |
Autoantigen-specific T cells have tissue-specific homing properties, suggesting that these cells may be ideal vehicles for the local delivery of immunoregulatory molecules. We tested this hypothesis by using type II collagen-specific (CII-specific) CD4(+) T hybridomas or primary CD4(+) T cells after gene transfer, as vehicles to deliver an immunoregulatory protein for the treatment of collagen-induced arthritis (CIA), a mouse model of rheumatoid arthritis (RA). CII-specific T cells or hybridomas were transduced using retroviral vectors to constitutively express the IL-12 antagonist, IL-12 p40. Transfer of engineered CD4(+) T cells after immunization significantly inhibited the development of CIA, while cells transduced with vector control had no effect. The beneficial effect on CIA of IL-12 p40-transduced T cells required TCR specificity against CII, since transfer of T cells specific for another antigen producing equivalent amounts of IL-12 p40 had no effect. In vivo cell detection using bioluminescent labels and RT-PCR showed that transferred CII-reactive T-cell hybridomas accumulated in inflamed joints in mice with CIA. These results indicate that the local delivery of IL-12 p40 by T cells inhibited CIA by suppressing autoimmune responses at the site of inflammation. Modifying antigen-specific T cells by retroviral transduction for local expression of immunoregulatory proteins thus offers a promising strategy for treating RA.
|
| 巻・号 |
107(10)
|
| ページ |
1293-301
|
| 公開日 |
2001-5-1
|
| DOI |
10.1172/JCI12037
|
| PMID |
11375419
|
| PMC |
PMC209299
|
| MeSH |
Adoptive Transfer
Animals
Arthritis, Rheumatoid / therapy*
Collagen / immunology*
Genetic Therapy / methods*
Hybridomas
Interleukin-12 / antagonists & inhibitors
Male
Mice
Mice, Inbred DBA
Retroviridae / genetics
T-Lymphocyte Subsets / immunology*
T-Lymphocyte Subsets / transplantation
|
| IF |
11.864
|
| 引用数 |
141
|
|
WOS 分野
|
MEDICINE, RESEARCH & EXPERIMENTAL
|
| リソース情報 |
| 遺伝子材料 |
pMFGmIL12p40 (RDB1447) |
