Disruption of T cell suppression in chronic lymphocytic leukemia by CD200 blockade.
CD200 plays a key role in regulating the immune system and has been shown to be upregulated on the surface of different tumors including chronic lymphocytic leukemia. In this study we addressed the effects of CD200 over-expression in CLL cells on autologous T cells in a mixed lymphocyte reaction system. We used native and CD40 ligand (CD40L)-stimulated CLL cells as antigen-presenting cells (APCs) to expand autologous T cells of 14 patients. T cell proliferation over 3 weeks of in vitro culture was significantly enhanced compared to control cells when using CD40L-stimulated APCs and the anti-CD200 antibody 1B9 (p=0.0004). CD200 blockade was further shown to stimulate antigen-specific T cell responses towards the CLL-associated antigen fibromodulin (p=0.04). Finally, the number of CD4+/CD25high/FOXP3+ T cells (T(reg)) was significantly decreased adding anti-CD200 antibody (p=0.04). In summary, CD200 blockade may provide therapeutic benefits in CLL by augmenting an antigen-specific T cell response with suppression of regulatory T cells.
Laboratory of Cellular Immunotherapy, Clinic I of Internal Medicine, University of Cologne, Germany.
Christian P
CP
Pallasch
Sabine
S
Ulbrich
Reinhild
R
Brinker
Michael
M
Hallek
Robert A
RA
Uger
Clemens-Martin
CM
Wendtner
D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D000938:Antigen-Presenting Cells; D015703:Antigens, CD / Q000276:immunology*; D000951:Antigens, Neoplasm; D049109:Cell Proliferation; D016326:Extracellular Matrix Proteins / Q000276:immunology; D000071235:Fibromodulin; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy* / Q000276:immunology*; D011509:Proteoglycans / Q000276:immunology; D037182:T-Cell Antigen Receptor Specificity; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000951:Antigens, Neoplasm; D016326:Extracellular Matrix Proteins; C000604330:FMOD protein, human; D011509:Proteoglycans; D000071235:Fibromodulin; C042739:antigens, CD200