This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Ishida, T. Articles by Ueda, R. Search for Related Content PubMed PubMed Citation Articles by Ishida, T. Articles by Ueda, R.

Specific Recruitment of CC Chemokine Receptor 4–Positive Regulatory T Cells in Hodgkin Lymphoma Fosters Immune Privilege

Departments of ¹ Internal Medicine and Molecular Science and ² Clinical Pathology, Nagoya City University Graduate School of Medical Sciences, Kawasumi, Mizuho-chou, Mizuho-ku, Nagoya-shi, Aichi, Japan

Requests for reprints: Takashi Ishida, Department of Internal Medicine and Molecular Science, Nagoya City University Graduate School of Medical Sciences, 1 Kawasumi, Mizuho-chou, Mizuho-ku, Nagoya, Aichi 467-8601, Japan. Phone: 81-52-853-8216; Fax: 81-52-852-0849; E-mail: itakashi{at}med.nagoya-cu.ac.jp.

Hodgkin lymphoma (HL) is characterized by the presence of a small number of tumor cells in a rich background of inflammatory cells, but the contribution of the abundant nontumor cells to HL pathogenesis is poorly understood. We showed that migratory CD4⁺ cells induced by HL cells were hyporesponsive to T-cell receptor stimulation and suppressed the activation/proliferation of the effector CD4⁺ T cells in an autologous setting. We further showed that HL cells in the affected lymph nodes were surrounded by a large number of lymphocytes expressing both CC chemokine receptor 4 (CCR4) and FOXP3. These findings indicate that the migratory cells induced by HL cells function as regulatory T (Treg) cells so that these cells create a favorable environment for the tumor cells to escape from host immune system. In addition, we showed that a chimeric anti-CCR4 monoclonal antibody (mAb) could deplete CCR4⁺ T cells and inhibit the migration of CD4⁺CD25⁺ T cells in vitro. Recognition of the importance of CCR4⁺ Treg cells in the pathogenesis of HL will allow rational design of more effective treatments, such as use of an anti-CCR4 mAb, to overcome the suppressive effect of CCR4⁺ Treg cells on the host immune response to tumor cells. (Cancer Res 2006; 66(11): 5716-22)

This article has been cited by other articles:

				B. Lamprecht, S. Kreher, I. Anagnostopoulos, K. Johrens, G. Monteleone, F. Jundt, H. Stein, M. Janz, B. Dorken, and S. Mathas Aberrant expression of the Th2 cytokine IL-21 in Hodgkin lymphoma cells regulates STAT3 signaling and attracts Treg cells via regulation of MIP-3{alpha} Blood, October 15, 2008; 112(8): 3339 - 3347. [Abstract] [Full Text] [PDF]

				P. E. M. Patten, A. G. S. Buggins, J. Richards, A. Wotherspoon, J. Salisbury, G. J. Mufti, T. J. Hamblin, and S. Devereux CD38 expression in chronic lymphocytic leukemia is regulated by the tumor microenvironment Blood, May 15, 2008; 111(10): 5173 - 5181. [Abstract] [Full Text] [PDF]

				Y. Ma, L. Visser, H. Roelofsen, M. de Vries, A. Diepstra, G. van Imhoff, T. van der Wal, M. Luinge, G. Alvarez-Llamas, H. Vos, et al. Proteomics analysis of Hodgkin lymphoma: identification of new players involved in the cross-talk between HRS cells and infiltrating lymphocytes Blood, February 15, 2008; 111(4): 2339 - 2346. [Abstract] [Full Text] [PDF]

				S. Deola, M. C. Panelli, D. Maric, S. Selleri, N. I. Dmitrieva, C. Y. Voss, H. Klein, D. Stroncek, E. Wang, and F. M. Marincola Helper B Cells Promote Cytotoxic T Cell Survival and Proliferation Independently of Antigen Presentation through CD27/CD70 Interactions J. Immunol., February 1, 2008; 180(3): 1362 - 1372. [Abstract] [Full Text] [PDF]

				J. Haas, L. Schopp, B. Storch-Hagenlocher, B. Fritzsching, C. Jacobi, L. Milkova, B. Fritz, A. Schwarz, E. Suri-Payer, M. Hensel, et al. Specific recruitment of regulatory T cells into the CSF in lymphomatous and carcinomatous meningitis Blood, January 15, 2008; 111(2): 761 - 766. [Abstract] [Full Text] [PDF]

				H. Yano, T. Ishida, A. Inagaki, T. Ishii, J. Ding, S. Kusumoto, H. Komatsu, S. Iida, H. Inagaki, and R. Ueda Defucosylated Anti CC Chemokine Receptor 4 Monoclonal Antibody Combined with Immunomodulatory Cytokines: A Novel Immunotherapy for Aggressive/Refractory Mycosis Fungoides and Sezary Syndrome Clin. Cancer Res., November 1, 2007; 13(21): 6494 - 6500. [Abstract] [Full Text] [PDF]

				Z.-Z. Yang, A. J. Novak, S. C. Ziesmer, T. E. Witzig, and S. M. Ansell CD70+ non-Hodgkin lymphoma B cells induce Foxp3 expression and regulatory function in intratumoral CD4+CD25 T cells Blood, October 1, 2007; 110(7): 2537 - 2544. [Abstract] [Full Text] [PDF]

				T. Tanijiri, T. Shimizu, K. Uehira, T. Yokoi, H. Amuro, H. Sugimoto, Y. Torii, K. Tajima, T. Ito, R. Amakawa, et al. Hodgkin's Reed-Sternberg cell line (KM-H2) promotes a bidirectional differentiation of CD4+CD25+Foxp3+ T cells and CD4+ cytotoxic T lymphocytes from CD4+ naive T cells J. Leukoc. Biol., September 1, 2007; 82(3): 576 - 584. [Abstract] [Full Text] [PDF]

				P. Juszczynski, J. Ouyang, S. Monti, S. J. Rodig, K. Takeyama, J. Abramson, W. Chen, J. L. Kutok, G. A. Rabinovich, and M. A. Shipp The AP1-dependent secretion of galectin-1 by Reed Sternberg cells fosters immune privilege in classical Hodgkin lymphoma PNAS, August 7, 2007; 104(32): 13134 - 13139. [Abstract] [Full Text] [PDF]

				J. H. Lee, S. G. Kang, and C. H. Kim FoxP3+ T Cells Undergo Conventional First Switch to Lymphoid Tissue Homing Receptors in Thymus but Accelerated Second Switch to Nonlymphoid Tissue Homing Receptors in Secondary Lymphoid Tissues J. Immunol., January 1, 2007; 178(1): 301 - 311. [Abstract] [Full Text] [PDF]