Document Detail

Specific recruitment of CC chemokine receptor 4-positive regulatory T cells in Hodgkin lymphoma fosters immune privilege.
MedLine Citation:
PMID:  16740709     Owner:  NLM     Status:  MEDLINE    
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.
Takashi Ishida; Toshihiko Ishii; Atsushi Inagaki; Hiroki Yano; Hirokazu Komatsu; Shinsuke Iida; Hiroshi Inagaki; Ryuzo Ueda
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Cancer research     Volume:  66     ISSN:  0008-5472     ISO Abbreviation:  Cancer Res.     Publication Date:  2006 Jun 
Date Detail:
Created Date:  2006-06-02     Completed Date:  2006-07-27     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  2984705R     Medline TA:  Cancer Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  5716-22     Citation Subset:  IM    
Department of Internal Medicine and Molecular Science and Clinical Pathology, Nagoya City University Graduate School of Medical Sciences, Kawasumi, Mizuho-chou, Mizuho-ku, Nagoya-shi, Aichi, Japan.
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MeSH Terms
Antibodies, Monoclonal / immunology,  pharmacology
Cell Line, Tumor
Cell Movement / immunology
Chemokine CCL17
Chemokines / biosynthesis,  immunology
Chemokines, CC / biosynthesis,  immunology
Flow Cytometry
Forkhead Transcription Factors / biosynthesis,  immunology
Hodgkin Disease / immunology*
Lymphocyte Activation
Lymphoma, Large B-Cell, Diffuse / immunology
Receptors, CCR4
Receptors, Chemokine / biosynthesis,  immunology*
Receptors, Interleukin-2 / immunology
T-Lymphocytes, Regulatory / immunology*
Reg. No./Substance:
0/Antibodies, Monoclonal; 0/CCL17 protein, human; 0/CCR4 protein, human; 0/Chemokine CCL17; 0/Chemokines; 0/Chemokines, CC; 0/FOXP3 protein, human; 0/Forkhead Transcription Factors; 0/Receptors, CCR4; 0/Receptors, Chemokine; 0/Receptors, Interleukin-2

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