Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents

This Article Full Text Full Text (PDF, 166K) PPT slides of all figures Alert me when this article is cited Citation Map Services Email this article Similar articles in this journal Similar articles in PubMed Alert me to new content in the JEM Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Ogg, G. S. Articles by Cerundolo, V. Search for Related Content PubMed PubMed Citation Articles by Ogg, G. S. Articles by Cerundolo, V. Pubmed/NCBI databases Substance via MeSH Medline Plus Health Information Autoimmune Diseases Vitiligo Social Bookmarking                            What's this?

Brief Definitive Reports

Graham S. Ogg^*, P. Rod Dunbar^*, Pedro Romero, Ji-Li Chen^*, and Vincenzo Cerundolo^*

From the ^* Institute of Molecular Medicine, Nuffield Department of Clinical Medicine, Oxford, OX3 9DS, United Kingdom; and the Ludwig Institute for Cancer Research, Lausanne Branch, University of Lausanne, Epalinges, 1011 Switzerland

Vitiligo is an autoimmune condition characterized by loss of epidermal melanocytes. Using tetrameric complexes of human histocompatibility leukocyte antigen (HLA) class I to identify antigen-specific T cells ex vivo, we observed high frequencies of circulating MelanA-specific, A*0201-restricted cytotoxic T lymphocytes (A2–MelanA tetramer⁺ CTLs) in seven of nine HLA-A*0201–positive individuals with vitiligo. Isolated A2–MelanA tetramer⁺ CTLs were able to lyse A*0201-matched melanoma cells in vitro and their frequency ex vivo correlated with extent of disease. In contrast, no A2–MelanA tetramer⁺ CTL could be identified ex vivo in all four A*0201-negative vitiligo patients or five of six A*0201-positive asymptomatic controls. Finally, we observed that the A2–MelanA tetramer⁺ CTLs isolated from vitiligo patients expressed high levels of the skin homing receptor, cutaneous lymphocyte-associated antigen, which was absent from the CTLs seen in the single A*0201-positive normal control. These data are consistent with a role of skin-homing autoreactive melanocyte-specific CTLs in causing the destruction of melanocytes seen in autoimmune vitiligo. Lack of homing receptors on the surface of autoreactive CTLs could be a mechanism to control peripheral tolerance in vivo.

Key Words: human • skin • cytotoxic T lymphocytes • fluorescence-activated cell sorter • autoimmunity

Abbreviations used: CLA, cutaneous lymphocyte-associated antigen.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Facebook    Reddit    Technorati    Twitter    What's this?

This article has been cited by other articles:

• Bradley, V., Kemp, E. H., Dickinson, C., Key, T., Gibbs, P., Clatworthy, M. R. (2009). Vitiligo following a combined liver-kidney transplant. Nephrol Dial Transplant 24: 686-688 [Abstract] [Full Text]  
• Seneviratne, S.L., Black, A.P., Jones, L., Bailey, A.S., Ogg, G.S. (2007). The role of skin-homing T cells in extrinsic atopic dermatitis. QJM 100: 19-27 [Abstract] [Full Text]  
• Lambe, T., Leung, J. C. H., Bouriez-Jones, T., Silver, K., Makinen, K., Crockford, T. L., Ferry, H., Forrester, J. V., Cornall, R. J. (2006). CD4 T Cell-Dependent Autoimmunity against a Melanocyte Neoantigen Induces Spontaneous Vitiligo and Depends upon Fas-Fas Ligand Interactions.. J. Immunol. 177: 3055-3062 [Abstract] [Full Text]  
• Boonman, Z. F. H. M., van Mierlo, G. J. D., Fransen, M. F., de Keizer, R. J. W., Jager, M. J., Melief, C. J. M., Toes, R. E. M. (2005). Maintenance of Immune Tolerance Depends on Normal Tissue Homeostasis. J. Immunol. 175: 4247-4254 [Abstract] [Full Text]  
• Friese, M. A., Fugger, L. (2005). Autoreactive CD8+ T cells in multiple sclerosis: a new target for therapy?. Brain 128: 1747-1763 [Abstract] [Full Text]  
• Grimes, P. E. (2005). New Insights and New Therapies in Vitiligo. JAMA 293: 730-735 [Full Text]  
• Olsson, M. J. (2004). What Are the Needs for Transplantation Treatment in Vitiligo, and How Good Is It?. Arch Dermatol 140: 1273-1274 [Full Text]  
• Lengagne, R., Le Gal, F.-A., Garcette, M., Fiette, L., Ave, P., Kato, M., Briand, J.-P., Massot, C., Nakashima, I., Renia, L., Guillet, J.-G., Prevost-Blondel, A. (2004). Spontaneous Vitiligo in an Animal Model for Human Melanoma: Role of Tumor-specific CD8+ T Cells. Cancer Res. 64: 1496-1501 [Abstract] [Full Text]  
• Panagiotopoulos, C., Qin, H., Tan, R., Verchere, C. B. (2003). Identification of a {beta}-Cell-Specific HLA Class I Restricted Epitope in Type 1 Diabetes. Diabetes 52: 2647-2651 [Abstract] [Full Text]  
• Nagorsen, D., Scheibenbogen, C., Marincola, F. M., Letsch, A., Keilholz, U. (2003). Natural T Cell Immunity against Cancer. Clin. Cancer Res. 9: 4296-4303 [Abstract] [Full Text]  
• Parmiani, G., Pilla, L., Castelli, C., Rivoltini, L. (2003). Vaccination of patients with solid tumours. Ann Oncol 14: 817-824 [Abstract] [Full Text]  
• Mantovani, S., Palermo, B., Garbelli, S., Campanelli, R., Robustelli della Cuna, G., Gennari, R., Benvenuto, F., Lantelme, E., Giachino, C. (2002). Dominant TCR-{alpha} Requirements for a Self Antigen Recognition in Humans. J. Immunol. 169: 6253-6260 [Abstract] [Full Text]  
• Rubio-Godoy, V., Dutoit, V., Zhao, Y., Simon, R., Guillaume, P., Houghten, R., Romero, P., Cerottini, J.-C., Pinilla, C., Valmori, D. (2002). Positional Scanning-Synthetic Peptide Library-Based Analysis of Self- and Pathogen-Derived Peptide Cross-Reactivity with Tumor-Reactive Melan-A-Specific CTL. J. Immunol. 169: 5696-5707 [Abstract] [Full Text]  
• Fodor, J., Kawakami, Y., Kiniwa, Y. (2002). Correspondence re: Y. Kiniwa et al., Tumor Antigens Isolated from a Patient with Vitiligo and T-Cell-infiltrated Melanoma. Cancer Res., 61: 7900-7907, 2001.. Cancer Res. 62: 4836-4837 [Full Text]  
• Jackman, S. H., Keerthy, S., Perry, G. (2002). Murine Epidermal Cell Antigen (Skn)-Directed Autoimmunity Induced by Transfer of CD4+ T Cells. Annals of Clinical & Laboratory Science 32: 171-180 [Abstract] [Full Text]  
• Valmori, D., Scheibenbogen, C., Dutoit, V., Nagorsen, D., Asemissen, A. M., Rubio-Godoy, V., Rimoldi, D., Guillaume, P., Romero, P., Schadendorf, D., Lipp, M., Dietrich, P.-Y., Thiel, E., Cerottini, J.-C., Lienard, D., Keilholz, U. (2002). Circulating Tumor-reactive CD8+ T Cells in Melanoma Patients Contain a CD45RA+CCR7- Effector Subset Exerting ex Vivo Tumor-specific Cytolytic Activity. Cancer Res. 62: 1743-1750 [Abstract] [Full Text]  
• Zippelius, A., Pittet, M. J., Batard, P., Rufer, N., de Smedt, M., Guillaume, P., Ellefsen, K., Valmori, D., Lienard, D., Plum, J., MacDonald, H. R., Speiser, D. E., Cerottini, J.-C., Romero, P. (2002). Thymic Selection Generates a Large T Cell Pool Recognizing a Self-Peptide in Humans. JEM 195: 485-494 [Abstract] [Full Text]  
• Speiser, D. E., Colonna, M., Ayyoub, M., Cella, M., Pittet, M. J., Batard, P., Valmori, D., Guillaume, P., Lienard, D., Cerottini, J.-C., Romero, P. (2001). The Activatory Receptor 2B4 Is Expressed In Vivo by Human CD8+ Effector {alpha}{beta} T Cells. J. Immunol. 167: 6165-6170 [Abstract] [Full Text]  
• Kiniwa, Y., Fujita, T., Akada, M., Ito, K., Shofuda, T., Suzuki, Y., Yamamoto, A., Saida, T., Kawakami, Y. (2001). Tumor Antigens Isolated from a Patient with Vitiligo and T-Cell-infiltrated Melanoma. Cancer Res. 61: 7900-7907 [Abstract] [Full Text]  
• Millrain, M., Chandler, P., Dazzi, F., Scott, D., Simpson, E., Dyson, P. J. (2001). Examination of HY Response: T Cell Expansion, Immunodominance, and Cross-Priming Revealed by HY Tetramer Analysis. J. Immunol. 167: 3756-3764 [Abstract] [Full Text]  
• Sutmuller, R. P.M., van Duivenvoorde, L. M., van Elsas, A., Schumacher, T. N.M., Wildenberg, M. E., Allison, J. P., Toes, R. E.M., Offringa, R., Melief, C. J.M. (2001). Synergism of Cytotoxic T Lymphocyte-Associated Antigen 4 Blockade and Depletion of Cd25+ Regulatory T Cells in Antitumor Therapy Reveals Alternative Pathways for Suppression of Autoreactive Cytotoxic T Lymphocyte Responses. JEM 194: 823-832 [Abstract] [Full Text]  
• Jager, D, Jager, E, Knuth, A (2001). Immune responses to tumour antigens: implications for antigen specific immunotherapy of cancer. J. Clin. Pathol. 54: 669-674 [Abstract] [Full Text]  
• van Elsas, A., Sutmuller, R. P.M., Hurwitz, A. A., Ziskin, J., Villasenor, J., Medema, J.-P., Overwijk, W. W., Restifo, N. P., Melief, C. J.M., Offringa, R., Allison, J. P. (2001). Elucidating the Autoimmune and Antitumor Effector Mechanisms of a Treatment Based on Cytotoxic T Lymphocyte Antigen-4 Blockade in Combination with a B16 Melanoma Vaccine: Comparison of Prophylaxis and Therapy. JEM 194: 481-490 [Abstract] [Full Text]  
• Denkberg, G., Cohen, C. J., Reiter, Y. (2001). Critical Role for CD8 in Binding of MHC Tetramers to TCR: CD8 Antibodies Block Specific Binding of Human Tumor- Specific MHC-Peptide Tetramers to TCR. J. Immunol. 167: 270-276 [Abstract] [Full Text]  
• Schrama, D., Andersen, M. H., Terheyden, P., Schrøder, L., Pedersen, L. O., Straten, P. t., Becker, J. C. (2001). Oligoclonal T-Cell Receptor Usage of Melanocyte Differentiation Antigen-reactive T Cells in Stage IV Melanoma Patients. Cancer Res. 61: 493-496 [Abstract] [Full Text]  
• Smith, S. M., Brookes, R., Klein, M. R., Malin, A. S., Lukey, P. T., King, A. S., Ogg, G. S., Hill, A. V. S., Dockrell, H. M. (2000). Human CD8+ CTL Specific for the Mycobacterial Major Secreted Antigen 85A. J. Immunol. 165: 7088-7095 [Abstract] [Full Text]  
• Yee, C., Thompson, J. A., Roche, P., Byrd, D. R., Lee, P. P., Piepkorn, M., Kenyon, K., Davis, M. M., Riddell, S. R., Greenberg, P. D. (2000). Melanocyte Destruction after Antigen-Specific Immunotherapy of Melanoma: Direct Evidence of T Cell-Mediated Vitiligo. JEM 192: 1637-1644 [Abstract] [Full Text]  
• Schreurs, M. W. J., Eggert, A. A. O., de Boer, A. J., Vissers, J. L. M., van Hall, T., Offringa, R., Figdor, C. G., Adema, G. J. (2000). Dendritic Cells Break Tolerance and Induce Protective Immunity against a Melanocyte Differentiation Antigen in an Autologous Melanoma Model. Cancer Res. 60: 6995-7001 [Abstract] [Full Text]  
• Bercovici, N., Duffour, M.-T., Agrawal, S., Salcedo, M., Abastado, J.-P. (2000). New Methods for Assessing T-Cell Responses. CVI 7: 859-864 [Full Text]  
• Nielsen, M.-B., Monsurro, V., Migueles, S. A., Wang, E., Perez-Diez, A., Lee, K.-H., Kammula, U., Rosenberg, S. A., Marincola, F. M. (2000). Status of Activation of Circulating Vaccine-Elicited CD8+ T Cells. J. Immunol. 165: 2287-2296 [Abstract] [Full Text]  
• Mortarini, R., Borri, A., Tragni, G., Bersani, I., Vegetti, C., Bajetta, E., Pilotti, S., Cerundolo, V., Anichini, A. (2000). Peripheral Burst of Tumor-specific Cytotoxic T Lymphocytes and Infiltration of Metastatic Lesions by Memory CD8+ T Cells in Melanoma Patients Receiving Interleukin 12. Cancer Res. 60: 3559-3568 [Abstract] [Full Text]  
• Baurain, J.-F., Colau, D., van Baren, N., Landry, C., Martelange, V., Vikkula, M., Boon, T., Coulie, P. G. (2000). High Frequency of Autologous Anti-Melanoma CTL Directed Against an Antigen Generated by a Point Mutation in a New Helicase Gene. J. Immunol. 164: 6057-6066 [Abstract] [Full Text]  
• Colella, T. A., Bullock, T. N.J., Russell, L. B., Mullins, D. W., Overwijk, W. W., Luckey, C. J., Pierce, R. A., Restifo, N. P., Engelhard, V. H. (2000). Self-Tolerance to the Murine Homologue of a Tyrosinase-Derived Melanoma Antigen: Implications for Tumor Immunotherapy. JEM 191: 1221-1232 [Abstract] [Full Text]  
• Lee, K.-H., Wang, E., Nielsen, M.-B., Wunderlich, J., Migueles, S., Connors, M., Steinberg, S. M., Rosenberg, S. A., Marincola, F. M. (1999). Increased Vaccine-Specific T Cell Frequency After Peptide-Based Vaccination Correlates with Increased Susceptibility to In Vitro Stimulation But Does Not Lead to Tumor Regression. J. Immunol. 163: 6292-6300 [Abstract] [Full Text]  
• Whelan, J. A., Dunbar, P. R., Price, D. A., Purbhoo, M. A., Lechner, F., Ogg, G. S., Griffiths, G., Phillips, R. E., Cerundolo, V., Sewell, A. K. (1999). Specificity of CTL Interactions with Peptide-MHC Class I Tetrameric Complexes Is Temperature Dependent. J. Immunol. 163: 4342-4348 [Abstract] [Full Text]  
• Speiser, D. E., Pittet, M. J., Valmori, D., Dunbar, R., Rimoldi, D., Lienard, D., MacDonald, H. R., Cerottini, J.-C., Cerundolo, V., Romero, P. (1999). In Vivo Expression of Natural Killer Cell Inhibitory Receptors by Human Melanoma-Specific Cytolytic T Lymphocytes. JEM 190: 775-782 [Abstract] [Full Text]  
• Anichini, A., Molla, A., Mortarini, R., Tragni, G., Bersani, I., Di Nicola, M., Gianni, A. M., Pilotti, S., Dunbar, R., Cerundolo, V., Parmiani, G. (1999). An Expanded Peripheral T Cell Population to a Cytotoxic T Lymphocyte (Ctl)-Defined, Melanocyte-Specific Antigen in Metastatic Melanoma Patients Impacts on Generation of Peptide-Specific Ctls but Does Not Overcome Tumor Escape from Immune Surveillance in Metastatic Lesions. JEM 190: 651-668 [Abstract] [Full Text]  
• Pittet, M. J., Valmori, D., Dunbar, P. R., Speiser, D. E., Lienard, D., Lejeune, F., Fleischhauer, K., Cerundolo, V., Cerottini, J.-C., Romero, P. (1999). High Frequencies of Naive Melan-a/Mart-1-Specific Cd8+ T Cells in a Large Proportion of Human Histocompatibility Leukocyte Antigen (Hla)-A2 Individuals. JEM 190: 705-716 [Abstract] [Full Text]  
• van Elsas, A., Hurwitz, A. A., Allison, J. P. (1999). Combination Immunotherapy of B16 Melanoma Using Anti-Cytotoxic T Lymphocyte-Associated Antigen 4 (Ctla-4) and Granulocyte/Macrophage Colony-Stimulating Factor (Gm-Csf)-Producing Vaccines Induces Rejection of Subcutaneous and Metastatic Tumors Accompanied by Autoimmune Depigmentation. JEM 190: 355-366 [Abstract] [Full Text]  
• Valmori, D., J. Pittet, M., Vonarbourg, C., Rimoldi, D., Lienard, D., Speiser, D., Dunbar, R., Cerundolo, V., Cerottini, J.-C., Romero, P. (1999). Analysis of the Cytolytic T Lymphocyte Response of Melanoma Patients to the Naturally HLA-A*0201-associated Tyrosinase Peptide 368-376. Cancer Res. 59: 4050-4055 [Abstract] [Full Text]  
• Dunbar, P. R., Chen, J.-L., Chao, D., Rust, N., Teisserenc, H., Ogg, G. S., Romero, P., Weynants, P., Cerundolo, V. (1999). Cutting Edge: Rapid Cloning of Tumor-Specific CTL Suitable for Adoptive Immunotherapy of Melanoma. J. Immunol. 162: 6959-6962 [Abstract] [Full Text]  

Home | Help | Feedback | Subscriptions | Archive | Search

TABLE OF CONTENTS