論文 - 詳細
| RRC ID | 11829 |
|---|---|
| 著者 | Schuler P, Contassot E, Irla M, Hugues S, Preynat-Seauve O, Beermann F, Donda A, French LE, Huard B. |
| タイトル | Direct presentation of a melanocyte-associated antigen in peripheral lymph nodes induces cytotoxic CD8+ T cells. |
| ジャーナル | Cancer Res |
| Abstract |
Encounter of self-antigens in the periphery by mature T cells induces tolerance in the steady-state. Hence, it is not understood why the same peripheral antigens are also promiscuously expressed in the thymus to mediate central tolerance. Here, we analyzed CD8(+) T-cell tolerance to such an antigen constituted by ovalbumin under the control of the tyrosinase promoter. As expected, endogenous CD8(+) T-cell responses were altered in the periphery of transgenic mice, resulting from promiscuous expression of the self-antigen in mature medullary epithelial cells and deletion of high-affinity T cells in the thymus. In adoptive T-cell transfer experiments, we observed constitutive presentation of the self-antigen in peripheral lymph nodes. Notably, this self-antigen presentation induced persisting cytotoxic cells from high-affinity CD8(+) T-cell precursors. Lymph node resident melanoblasts expressing tyrosinase directly presented the self-antigen to CD8(+) T cells, independently of bone marrow-derived antigen-presenting cells. This peripheral priming was independent of the subcellular localization of the self-antigen, indicating that this mechanism may apply to other melanocyte-associated antigens. Hence, central tolerance by promiscuous expression of peripheral antigens is a mandatory, rather than a superfluous, mechanism to counteract the peripheral priming, at least for self-antigens that can be directly presented in lymph nodes. The peripheral priming by lymph node melanoblasts identified here may constitute an advantage for immunotherapies based on adoptive T-cell transfer. |
| 巻・号 | 68(20) |
| ページ | 8410-8 |
| 公開日 | 2008-10-15 |
| DOI | 10.1158/0008-5472.CAN-08-0809 |
| PII | 68/20/8410 |
| PMID | 18922914 |
| MeSH | Animals Antigen Presentation* Autoantigens / immunology* Immunotherapy Lymph Nodes / immunology* Melanocytes / immunology* Melanoma / therapy Mice Mice, Inbred C57BL Mice, Inbred DBA Ovalbumin / genetics Ovalbumin / immunology T-Lymphocytes, Cytotoxic / immunology* |
| IF | 9.727 |
| 引用数 | 9 |
| WOS 分野 | ONCOLOGY |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 各媒体での言及数の合計 | 0 |
| リソース情報 | |
| 実験動物マウス | RBRC01888 RBRC01896 |