The role of CD200 in immunity to B cell lymphoma.
CD200 is a transmembrane protein broadly expressed on a variety of cell types, which delivers immunoregulatory signals through binding to receptors (CD200Rs) expressed on monocytes/myeloid cells and T lymphocytes. Signals delivered through the CD200:CD200R axis have been shown to play an important role in the regulation of anti-tumor immunity, and overexpression of CD200 has been reported in a number of malignancies, including CLL, as well as on cancer stem cells. We investigated the effect of CD200 blockade in vitro on a generation of CTL responses against a poorly immunogenic CD200+ lymphoma cell line and fresh cells obtained from CLL patients using anti-CD200 mAb and CD200-specific siRNAs. Suppression of functional expression of CD200 augmented killing of the CD200+ cells, as well as production of the inflammatory cytokines IFN-gamma and TNF-alpha by effector PBMCs. Killing was mediated by CD8+ cytotoxic T cells, and CD4+ T cells play an important role in CD200-mediated suppression of CTL responses. Our data suggest that CD200 blockade may represent a novel approach to clinical treatment of CLL.
Wong
Karrie K
KK
Institute of Medical Science, University Health Network, University of Toronto, Rm. 2-805, MaRS Tower, 101 College St., Toronto, ON, Canada, M5G1L7.
Khatri
Ismat
I
Shaha
Suchinta
S
Spaner
David E
DE
Gorczynski
Reginald M
RM
D000911:Antibodies, Monoclonal / Q000494:pharmacology; D015703:Antigens, CD / Q000187:drug effects / Q000276:immunology*; D045744:Cell Line, Tumor; D016207:Cytokines / Q000096:biosynthesis; D003602:Cytotoxicity, Immunologic; D006801:Humans; D007109:Immunity; D016393:Lymphoma, B-Cell / Q000276:immunology*; D034741:RNA, Small Interfering / Q000494:pharmacology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D016207:Cytokines; D034741:RNA, Small Interfering; C042739:antigens, CD200