RRC ID 11829
Author Schuler P, Contassot E, Irla M, Hugues S, Preynat-Seauve O, Beermann F, Donda A, French LE, Huard B.
Title Direct presentation of a melanocyte-associated antigen in peripheral lymph nodes induces cytotoxic CD8+ T cells.
Journal 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.
Volume 68(20)
Pages 8410-8
Published 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 9.13
Times Cited 8
Mice C57BL/6-Wsh/Wsh