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Blood, 1 May 2006, Vol. 107, No. 9, pp. 3639-3646. Prepublished online as a Blood First Edition Paper on January 10, 2006; DOI 10.1182/blood-2005-08-3376. This Article Full Text Full Text (PDF) All Versions of this Article: 2005-08-3376v1 107/9/3639    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 Yang, Z.-Z. Articles by Ansell, S. M. Search for Related Content PubMed PubMed Citation Articles by Yang, Z.-Z. Articles by Ansell, S. M. Related Collections Immunobiology Neoplasia Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY Intratumoral CD4+CD25+ regulatory T-cell-mediated suppression of infiltrating CD4+ T cells in B-cell non-Hodgkin lymphoma Zhi-Zhang Yang, Anne J. Novak, Mary J. Stenson, Thomas E. Witzig, and Stephen M. Ansell From the Division of Hematology and Internal Medicine, Mayo Clinic College of Medicine, Rochester, MN. Most non-Hodgkin lymphomas (NHLs) are of B-cell origin, but the tumor tissue can be variably infiltrated with T cells. In the present study, we have identified a subset of CD4+CD25+ T cells with high levels of CTLA-4 and Foxp3 (intratumoral Treg cells) that are overrepresented in biopsy specimens of B-cell NHL (median of 17% in lymphoma biopsies, 12% in inflammatory tonsil, and 6% in tumor-free lymph nodes; P = .001). We found that these CD4+CD25+ T cells suppressed the proliferation and cytokine (IFN- and IL-4) production of infiltrating CD4+CD25- T cells in response to PHA stimulation. PD-1 was found to be constitutively and exclusively expressed on a subset of infiltrating CD4+CD25- T cells, and B7-H1 could be induced on intratumoral CD4+CD25+ T cells in B-cell NHL. Anti-B7-H1 antibody or PD-1 fusion protein partly restored the proliferation of infiltrating CD4+CD25- T cells when cocultured with intratumoral Treg cells. Finally, we found that CCL22 secreted by lymphoma B cells is involved in the chemotaxis and migration of intratumoral Treg cells that express CCR4, but not CCR8. Taken together, our results suggest that Treg cells are highly represented in the area of B-cell NHL and that malignant B cells are involved in the recruitment of these cells into the area of lymphoma. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? 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