Effects of dendritic cell and subgroup changes on bone marrow transplantation treatment of multiple

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BACKGROUND: Bone marrow transplantation is an effective treatment for severe forms of various autoimmune disorders. Dendritic cell reconstitution is thought to be one factor contributing to host immune recovery and therapeutic efficacy.OBJECTIVE: To assess the effects of bone marrow transplantation on an animal model of experimental autoimmune encephalomyelitis (EAE), and to investigate changes in dendritic cells and subgroups following bone marrow transplantation.DESIGN, TIME AND SETTING: This experimental, neuroimmunological study was performed in Sun Yat-sen University between August 2006 and May 2007.MATERIALS: A total of 30 female C57BL/6 mice, aged 6-8 weeks, served as recipients, and 20 female adult C57BL/6 served as donors. Myelin oligodendrocyte glycoprotein 35-55 amino acid peptide (MOG35-55) of murine origin was synthesized by Bio-Scientific (Xi'an, China, purity > 95%). Complete Freund's adjuvant was purchased from Difco Laboratories, Detroit, MI; pertussis vaccine was purchased from Alexis, San Diego, CA; radiation device and flow cytometry for FACS analysis were purchased from Theratron 780-C, Canada and Coulter, Fullerton, CA, respectively.METHODS: The C57BL/6 mice, aged 6-8 weeks, were immunized by subcutaneous injection of MOG35-55 peptide emulsified in complete Freund's adjuvant, which contained 500 μg Mycobacterium tuberculosis H37RA. The mice were subsequently intravenously injected with pertussis vaccine to induce EAE. The mice were randomly assigned to transplantation and EAE model groups (n = 12 for each). Bone marrow cells [(5-10) × 10~6] were transplanted into EAE mice via the tail vein 4-6 hours following total body irradiation, and the model group was not treated.MAIN OUTCOME MEASURES: Mouse behavioral changes following EAE were evaluated daily. Injured spinal cord tissue sections were stained with hematoxylin and eosin 20 days after the initial immunization to observe inflammatory infiltration using light microscopy. Flow cytometry was used to detect the ratio and absolute number of DC1 (CD8a~-CD11c~+) and DC2 (CD8a~+CD11c~+) in peripheral blood 36 days after bone marrow transplantation.RESULTS: Significant improvement in clinical signs was observed in EAE mice following bone marrow transplantation compared with the model group (P < 0.01), as well as attenuated lymphocyte and macrophage infiltration. Compared with the model group, the absolute number of dendritic cells and DC1, as well as the DC1/DC2 ratio, was significantly greater following bone marrow transplantation (P < 0.05 or P < 0.01).CONCLUSION: The increased proportion of dendritic cells and DC1 is proposed to contribute to EAE remission following bone marrow transplantation.
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