Aberrant CD200/CD200R1 expression and function in systemic lupus erythematosus contributes to abnormal T cell responsiveness and dendritic cell activity Full Text
Arthritis Research & Therapy, 05/24/2012
Li Y et al. – CD200 and CD200R1 expression and function are abnormal in systemic lupus erythematosus (SLE) and may contribute to the immunologic abnormalities in SLE.Methods
- Serum CD200 level was detected by ELISA.
- The expression of CD200/CD200R1 by CD4+ T cells and dendritic cells (DCs) was examined by flow cytometry, then compared between SLE patients and healthy controls (HCs).
- Peripheral blood mononuclear cells were stained with Carboxyfluorescein Diacetate Succinimidyl Ester (CFSE) and Annexin V/propidium iodide for evaluation of the effect of CD200 on cell proliferation and apoptosis.
- In addition, the effect of CD200 on DC function was determined by transwell migration assay as well as by measurement of binding and phagocytosis of apoptotic cells.
- In SLE patients, the number of CD200+ cells and the level of soluble CD200 were significantly higher than in HCs, whereas the expression of CD200R1 by CD4+T cells and DCs was decreased.
- Furthermore, the increased CD200 expression by early apoptotic cells contributed to their diminished binding and phagocytosis by DCs in SLE.
- Importantly, the engagement of CD200 receptor on CD4+ T cells with CD200–Fc fusion protein in vitro reduced the differentiation of T helper 17 (Th17) cells and reversed the defective induction of CD4+CD25highFoxP3+ T cells by transforming growth factor beta (TGFbeta) in SLE patients.
- Conversely, blockade of CD200–CD200R1 interaction with anti–CD200R1 antibody promoted CD4+ T cell proliferation.