Journal
LEUKEMIA RESEARCH
Volume 33, Issue 3, Pages 460-464Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.leukres.2008.08.021
Keywords
CD200; Chronic lymphocytic leukemia; Tumor-associated antigen; Fibromodulin; Regulatory T cells
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Funding
- Deutsche Jose Carreras Leukamie Stiftung [DJCLS R06/16]
- Koln Fortune [050808]
- Trillium Therapeutics Inc., Toronto, Canada
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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. (c) 2008 Elsevier Ltd. All rights reserved.
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