Expression of the Epstein-Barr virus-encoded Epstein-Barr virus nuclear antigen 1 in Hodgkin's lymphoma cells mediates Up-regulation of CCL20 and the migration of regulatory T cells. Export

@article{citeulike:5982440, abstract = {In approximately 50\% of patients with Hodgkin's lymphoma (HL), the Epstein-Barr virus (EBV), an oncogenic herpesvirus, is present in tumor cells. After microarray profiling of both HL tumors and cell lines, we found that EBV infection increased the expression of the chemokine CCL20 in both primary Hodgkin and Reed-Sternberg cells and Hodgkin and Reed-Sternberg cell-derived cell lines. Additionally, this up-regulation could be mediated by the EBV nuclear antigen 1 protein. The higher levels of CCL20 in the supernatants of EBV-infected HL cell lines increased the migration of CD4(+) lymphocytes that expressed FOXP3, a marker of regulatory T cells (Tregs), which are specialized CD4(+) T cells that inhibit effector CD4(+) and CD8(+) T cells. In HL, an increased number of Tregs is associated with the loss of EBV-specific immunity. Our results identify a mechanism by which EBV can recruit Tregs to the microenvironment of HL by inducing the expression of CCL20 and, by doing so, prevent immune responses against the virus-infected tumor population. Further investigation of how EBV recruits and modifies Tregs will contribute not only to our understanding of the pathogenesis of virus-associated tumors but also to the development of therapeutic strategies designed to manipulate Treg activity.}, author = {Baumforth, Karl R. and Birgersdotter, Anna and Reynolds, Gary M. and Wei, Wenbin and Kapatai, Georgia and Flavell, Joanne R. and Kalk, Emma and Piper, Karen and Lee, Steve and Machado, Lee and Hadley, Kerry and Sundblad, Anne and Sjoberg, Jan and Bjorkholm, Magnus and Porwit, Anna A. and Yap, Lee-Fah F. and Teo, Soohwang and Grundy, Richard G. and Young, Lawrence S. and Ernberg, Ingemar and Woodman, Ciaran B. and Murray, Paul G.}, citeulike-article-id = {5982440}, citeulike-linkout-0 = {http://dx.doi.org/10.2353/ajpath.2008.070845}, citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/18502823}, citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=18502823}, doi = {10.2353/ajpath.2008.070845}, issn = {1525-2191}, journal = {The American journal of pathology}, keywords = {cd4\_lymphocytes, cd8\_t\_cells, ebv, epstein\_barr\_virus, herpesvirus, hodgkin\_s\_lymphoma, immune\_responses, immunity, lymphoma, lymphoma\_cells, marker, microenvironment, nuclear\_antigen, pathogenesis, reed\_sternberg\_cell, reed\_sternberg\_cells, regulatory\_t\_cells, therapeutic\_strategies, tumor\_cells, tumors, virus\_ebv}, month = {July}, number = {1}, pages = {195--204}, posted-at = {2009-10-21 18:44:23}, priority = {5}, title = {Expression of the Epstein-Barr virus-encoded Epstein-Barr virus nuclear antigen 1 in Hodgkin's lymphoma cells mediates Up-regulation of CCL20 and the migration of regulatory T cells.}, url = {http://dx.doi.org/10.2353/ajpath.2008.070845}, volume = {173}, year = {2008} }

TY - JOUR ID - citeulike:5982440 L3 - citeulike-article-id:5982440 N2 - In approximately 50% of patients with Hodgkin's lymphoma (HL), the Epstein-Barr virus (EBV), an oncogenic herpesvirus, is present in tumor cells. After microarray profiling of both HL tumors and cell lines, we found that EBV infection increased the expression of the chemokine CCL20 in both primary Hodgkin and Reed-Sternberg cells and Hodgkin and Reed-Sternberg cell-derived cell lines. Additionally, this up-regulation could be mediated by the EBV nuclear antigen 1 protein. The higher levels of CCL20 in the supernatants of EBV-infected HL cell lines increased the migration of CD4(+) lymphocytes that expressed FOXP3, a marker of regulatory T cells (Tregs), which are specialized CD4(+) T cells that inhibit effector CD4(+) and CD8(+) T cells. In HL, an increased number of Tregs is associated with the loss of EBV-specific immunity. Our results identify a mechanism by which EBV can recruit Tregs to the microenvironment of HL by inducing the expression of CCL20 and, by doing so, prevent immune responses against the virus-infected tumor population. Further investigation of how EBV recruits and modifies Tregs will contribute not only to our understanding of the pathogenesis of virus-associated tumors but also to the development of therapeutic strategies designed to manipulate Treg activity. IS - 1 JF - The American journal of pathology SN - 1525-2191 EP - 204 TI - Expression of the Epstein-Barr virus-encoded Epstein-Barr virus nuclear antigen 1 in Hodgkin's lymphoma cells mediates Up-regulation of CCL20 and the migration of regulatory T cells. VL - 173 SP - 195 KW - cd4_lymphocytes KW - cd8_t_cells KW - ebv KW - epstein_barr_virus KW - herpesvirus KW - hodgkin_s_lymphoma KW - immune_responses KW - immunity KW - lymphoma KW - lymphoma_cells KW - marker KW - microenvironment KW - nuclear_antigen KW - pathogenesis KW - reed_sternberg_cell KW - reed_sternberg_cells KW - regulatory_t_cells KW - therapeutic_strategies KW - tumor_cells KW - tumors KW - virus_ebv AU - Baumforth, Karl AU - Birgersdotter, Anna AU - Reynolds, Gary AU - Wei, Wenbin AU - Kapatai, Georgia AU - Flavell, Joanne AU - Kalk, Emma AU - Piper, Karen AU - Lee, Steve AU - Machado, Lee AU - Hadley, Kerry AU - Sundblad, Anne AU - Sjoberg, Jan AU - Bjorkholm, Magnus AU - Porwit, Anna AU - Yap, Lee-Fah AU - Teo, Soohwang AU - Grundy, Richard AU - Young, Lawrence AU - Ernberg, Ingemar AU - Woodman, Ciaran AU - Murray, Paul PY - 2008/07// UR - http://dx.doi.org/10.2353/ajpath.2008.070845 ER -