| 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
|
| リソース情報 |
| 実験動物マウス |
RBRC01888
RBRC01896 |
