Deletional self-tolerance to a melanocyte/melanoma antigen derived from tyrosinase is mediated by a radio-resistant cell in peripheral and mesenteric lymph nodes
| Autor: | Victor H. Engelhard, Clare L. Bennett, Yiming Chen, Bjoern E. Clausen, Lisa A. Nichols, Teresa A. Colella |
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| Přispěvatelé: | Other departments |
| Rok vydání: | 2007 |
| Předmět: |
Tyrosinase
Immunology Receptors Antigen T-Cell Mice Transgenic Melanocyte Biology CD8-Positive T-Lymphocytes Autoantigens Radiation Tolerance Mice Melanocyte differentiation Antigens Neoplasm T-Lymphocyte Subsets medicine Immunology and Allergy Cytotoxic T cell Mesenteric lymph nodes Animals Mesentery Antigen-presenting cell Lymph node Melanoma Monophenol Monooxygenase Reverse Transcriptase Polymerase Chain Reaction Cross-presentation Adoptive Transfer Immunohistochemistry Cell biology medicine.anatomical_structure Self Tolerance Radiation Chimera Melanocytes Lymph Nodes |
| Zdroj: | Journal of immunology (Baltimore, Md., 179(2), 993-1003. American Association of Immunologists |
| ISSN: | 0022-1767 |
| Popis: | Self-tolerance to melanocyte differentiation Ags limits the ability to generate therapeutic antimelanoma responses. However, the mechanisms responsible for CD8 T cell tolerance to these Ags are unknown. We have used a newly generated TCR-transgenic mouse to establish the basis of tolerance to one such Ag from tyrosinase. Despite expression of tyrosinase transcripts in the thymus, central deletion does not shape the tyrosinase-specific CD8 T cell repertoire. We demonstrate that this endogenously expressed melanocyte Ag is constitutively presented in both peripheral and mesenteric lymph nodes, leading to abortive activation and deletion of tyrosinase-specific CD8 T cells. Importantly, this Ag is not presented by either radio-sensitive dendritic cells, or by radio-resistant Langerhans cells. Thus, for this endogenous Ag, cross-tolerization does not appear to be an operative mechanism. Instead, we find radioresistant tyrosinase mRNA expression in lymphoid compartments where CD8 T cell deletion occurs. This suggests that direct presentation of tyrosinase by radio-resistant lymph node resident cells is entirely responsible for tolerance to this endogenous melanocyte differentiation Ag. |
| Databáze: | OpenAIRE |
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