CD4 T cell-dependent autoimmunity against a melanocyte neoantigen induces spontaneous vitiligo and depends upon Fas-Fas ligand interactions.
Better understanding of tolerance and autoimmunity toward melanocyte-specific Ags is needed to develop effective treatment for vitiligo and malignant melanoma; yet, a systematic assessment of these mechanisms has been hampered by the difficulty in tracking autoreactive T cells. To address this issue...
| Main Authors: | , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
2006
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| _version_ | 1797078725824610304 |
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| author | Lambe, T Leung, J Bouriez-Jones, T Silver, K Makinen, K Crockford, T Ferry, H Forrester, J Cornall, R |
| author_facet | Lambe, T Leung, J Bouriez-Jones, T Silver, K Makinen, K Crockford, T Ferry, H Forrester, J Cornall, R |
| author_sort | Lambe, T |
| collection | OXFORD |
| description | Better understanding of tolerance and autoimmunity toward melanocyte-specific Ags is needed to develop effective treatment for vitiligo and malignant melanoma; yet, a systematic assessment of these mechanisms has been hampered by the difficulty in tracking autoreactive T cells. To address this issue, we have generated transgenic mice that express hen egg lysozyme as a melanocyte-specific neoantigen. By crossing these animals to a hen egg lysozyme-specific CD4 TCR transgenic line we have been able to track autoreactive CD4+ T cells from their development in the thymus to their involvement in spontaneous autoimmune disease with striking similarity to human vitiligo vulgaris and Vogt-Koyanagi-Harada syndrome. Our findings show that CD4-dependent destruction of melanocytes is partially inhibited by blocking Fas-Fas ligand interactions and also highlights the importance of local control of autoimmunity, as vitiligo remains patchy and never proceeds to confluence even when Ag and autoreactive CD4+ T cells are abundant. Immune therapy to enhance or suppress melanocyte-specific T cells can be directed at a series of semiredundant pathways involving tolerance and cell death. |
| first_indexed | 2024-03-07T00:35:51Z |
| format | Journal article |
| id | oxford-uuid:81625b35-d226-4d53-afe7-2ebe052a61c0 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T00:35:51Z |
| publishDate | 2006 |
| record_format | dspace |
| spelling | oxford-uuid:81625b35-d226-4d53-afe7-2ebe052a61c02022-03-26T21:29:54ZCD4 T cell-dependent autoimmunity against a melanocyte neoantigen induces spontaneous vitiligo and depends upon Fas-Fas ligand interactions.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:81625b35-d226-4d53-afe7-2ebe052a61c0EnglishSymplectic Elements at Oxford2006Lambe, TLeung, JBouriez-Jones, TSilver, KMakinen, KCrockford, TFerry, HForrester, JCornall, RBetter understanding of tolerance and autoimmunity toward melanocyte-specific Ags is needed to develop effective treatment for vitiligo and malignant melanoma; yet, a systematic assessment of these mechanisms has been hampered by the difficulty in tracking autoreactive T cells. To address this issue, we have generated transgenic mice that express hen egg lysozyme as a melanocyte-specific neoantigen. By crossing these animals to a hen egg lysozyme-specific CD4 TCR transgenic line we have been able to track autoreactive CD4+ T cells from their development in the thymus to their involvement in spontaneous autoimmune disease with striking similarity to human vitiligo vulgaris and Vogt-Koyanagi-Harada syndrome. Our findings show that CD4-dependent destruction of melanocytes is partially inhibited by blocking Fas-Fas ligand interactions and also highlights the importance of local control of autoimmunity, as vitiligo remains patchy and never proceeds to confluence even when Ag and autoreactive CD4+ T cells are abundant. Immune therapy to enhance or suppress melanocyte-specific T cells can be directed at a series of semiredundant pathways involving tolerance and cell death. |
| spellingShingle | Lambe, T Leung, J Bouriez-Jones, T Silver, K Makinen, K Crockford, T Ferry, H Forrester, J Cornall, R CD4 T cell-dependent autoimmunity against a melanocyte neoantigen induces spontaneous vitiligo and depends upon Fas-Fas ligand interactions. |
| title | CD4 T cell-dependent autoimmunity against a melanocyte neoantigen induces spontaneous vitiligo and depends upon Fas-Fas ligand interactions. |
| title_full | CD4 T cell-dependent autoimmunity against a melanocyte neoantigen induces spontaneous vitiligo and depends upon Fas-Fas ligand interactions. |
| title_fullStr | CD4 T cell-dependent autoimmunity against a melanocyte neoantigen induces spontaneous vitiligo and depends upon Fas-Fas ligand interactions. |
| title_full_unstemmed | CD4 T cell-dependent autoimmunity against a melanocyte neoantigen induces spontaneous vitiligo and depends upon Fas-Fas ligand interactions. |
| title_short | CD4 T cell-dependent autoimmunity against a melanocyte neoantigen induces spontaneous vitiligo and depends upon Fas-Fas ligand interactions. |
| title_sort | cd4 t cell dependent autoimmunity against a melanocyte neoantigen induces spontaneous vitiligo and depends upon fas fas ligand interactions |
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