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Blood, 1 March 2004, Vol. 103, No. 5, pp. 1755-1762. Prepublished online as a Blood First Edition Paper on November 6, 2003; DOI 10.1182/blood-2003-07-2594. This Article Full Text Full Text (PDF) All Versions of this Article: 2003-07-2594v1 103/5/1755    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Marshall, N. A. Articles by Vickers, M. A. Search for Related Content PubMed PubMed Citation Articles by Marshall, N. A. Articles by Vickers, M. A. Related Collections Immunobiology Neoplasia Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY Immunosuppressive regulatory T cells are abundant in the reactive lymphocytes of Hodgkin lymphoma Neil A. Marshall, Linsey E. Christie, Laura R. Munro, Dominic J. Culligan, Peter W. Johnston, Robert N. Barker, and Mark A. Vickers From the Department of Medicine and Therapeutics, Department of Haematology, and Department of Pathology, University of Aberdeen, Aberdeen, United Kingdom. Although immunosuppression has long been recognized in Hodgkin lymphoma (HL), the underlying basis for the lack of an effective immune response against the tumor remains unclear. The aim was to test our hypothesis that regulatory T cells dominate involved lymph nodes. The approach was to assay CD4+ T-cell function in HL-infiltrating lymphocytes (HLILs) and paired peripheral blood mononuclear cells (PBMCs) of 24 patients. Strikingly, unlike PBMCs, HLILs were anergic to stimulation with mitogen, primary, or recall antigens, mounting no proliferative responses and only rare T-helper 1 (Th1) or Th2 cytokine responses. Mixing paired HLILs and PBMCs showed the anergic effect was dominant and suppressed PBMC responses. Furthermore, flow cytometry demonstrated that HLILs contained large populations of both interleukin-10 (IL-10)–secreting T-regulatory 1 (Tr1) and CD4+CD25+ regulatory T cells. We found evidence for 3 mechanisms of action implicated in the suppressive functions of regulatory T cells: the inhibition of PBMCs by HLILs was ameliorated by neutralizing IL-10, by preventing cell-to-cell contact, and by blocking anti–cytotoxic T lymphocyte–associated antigen 4 (anti–CTLA-4). Thus, HLILs are highly enriched for regulatory T cells, which induce a profoundly immunosuppressive environment and so provide an explanation for the ineffective immune clearance of Hodgkin-Reed Sternberg cells. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Regulatory T cells in Hodgkin lymphoma Sibrand Poppema Blood 2004 103: 1565-1566. [Full Text] [PDF] This article has been cited by other articles: K. R.N. Baumforth, A. Birgersdotter, G. M. Reynolds, W. Wei, G. Kapatai, J. R. Flavell, E. Kalk, K. Piper, S. Lee, L. Machado, et al. 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 Am. J. Pathol., July 1, 2008; 173(1): 195 - 204. [Abstract] [Full Text] [PDF] S. Mittal, N. A. Marshall, L. Duncan, D. J. Culligan, R. N. Barker, and M. A. 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