RESEARCH ARTICLE Upregulation of CD200 is associated with Foxp3 + regulatory T cell expansion and disease progression in acute myeloid leukemia Ali Memarian & Maryam Nourizadeh & Farimah Masoumi & Mina Tabrizi & Amir Hossein Emami & Kamran Alimoghaddam & Jamshid Hadjati & Mahroo Mirahmadian & Mahmood Jeddi-Tehrani Received: 19 September 2012 / Accepted: 30 October 2012 # International Society of Oncology and BioMarkers (ISOBM) 2012 Abstract Immunosuppression in acute myeloid leukemia (AML) is an important mechanism of tumor escape. CD200, as an immunosuppressive molecule, is overex- pressed in some hematological malignancies and it has also been shown to be an independent prognostic factor in AML. In the current study, simultaneous CD200 expression and Foxp3 + regulatory T cell levels were investigated in Iranian patients with AML by flow cytometry. We also assessed the effect of CD200–CD200R blockade on Th1 and T-reg cy- tokine production and T cell proliferation in autologous AML- and monocyte-DC mixed lymphocyte reactions (MLRs). ELISA assay was performed to detect IL-2, IL- 12, IFN-γ, IL-10, and TGF-β production in MLR super- natants. Expression of Foxp3, IL-10, and TGF-β mRNAs in MLRs were detected by real-time PCR. Our results demon- strated significant overexpression of CD200 (P 0 0.001) in association with higher frequencies of Foxp3 + T cells in AML patients (r 0 0.8, P <0.001). Blocking of CD200– CD200R interaction demonstrated a significant decrease in TGF-β and IL-10 expression in AML-DC MLRs and a significant increase in IL-12 and IFN-γ expression in monocyte-DC MLRs. Elevated T cell levels with lower Foxp3 intensity was also shown in CD200–CD200R- blocked MLRs. Expression of IL-10 mRNA declined sig- nificantly only in AML-DC MLRs where CD200–CD200R interaction was blocked and the same result was observed for TGF-β and Foxp3 mRNA in both AML- and monocyte- DC MLRs. These data present a significant role for CD200 in suppressing anti-tumor immune response through stimu- lation of regulatory mechanisms in AML patients and sug- gest that CD200 may have a prognostic value in this malignancy and its blockade may be used as a target for AML immunotherapy. Keywords CD200 . Acute myeloid leukemia . T-reg . Immunosuppression . Disease progression Introduction Acute myeloid leukemia (AML) is a hematopoietic malig- nancy of the myeloid lineage, characterized by increase of precursor cells in the bone marrow (BM) and peripheral blood (PB) [1]. Although chemotherapy is administered, more than 50 % of AML cases go into relapse [2–4]. Electronic supplementary material The online version of this article (doi:10.1007/s13277-012-0578-x) contains supplementary material, which is available to authorized users. A. Memarian : M. Nourizadeh : F. Masoumi : J. Hadjati : M. Mirahmadian (*) Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran 14155 e-mail: mirahmadian@sina.tums.ac.ir M. Tabrizi Department of Medical Genetics, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran A. H. Emami Clinic of Hematology and Oncology, Vali-Asr Hospital, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran K. Alimoghaddam Hematology, Oncology and Stem Cell Transplantation Research Center, Tehran University of Medical Sciences, Shariati Hospital, Tehran, Iran M. Jeddi-Tehrani Monoclonal Antibody Research Center, Avicenna Research Institute, Tehran, Iran Tumor Biol. DOI 10.1007/s13277-012-0578-x