Abstract: Objective To investigate the immune modulation effect of lymphocytes co-cultured with human cord blood derived-multipotent stem cells(CB-SCs) and further to explore their therapeutic potential for Alzheimer’s Disease (AD) model mice. Methods CB-SCs were isolated from human cord blood. Lymphocytes were isolated from the spleens of AD model mice. The lymphocytes were co-cultured with CB-SCs or cultured alone for 72 h. AD model mice were divided into experimental group and control group randomly, and then the experimental group mice were administrated with lymphocytes co-cultured with CB-SCs and control group were administrated with lymphocytes cultured alone by caudal vein injection. Then, the behavior experiment was carried out. The CD4+CD25+Foxp3+Tregs were detected by flow cytometry. The protein expression of TNF-αand IL-10 in peripheral blood was detected by ELISA, The mRNA expression of TNF-α and IL-10 in brain tissue was detected by PCR. The amyloid-β（Aβ）plaques were detected by immunohistochemistry. Results 1) There is spatial learning and memory improvement on experimental group. 2) The Aβ plaques of experimental group were decreased compared to the control group. 3) The percentage of CD4+CD25+Foxp3+Tregs in peripheral blood and IL-10 level in plasma were higher in experimental group compared to those in the control group（P ＜0.05）. The pro-inflammatory cytokines, TNF-α level in plasma of experimental group was lower than that in the control group（P ＜0.001）. 4) The mRNA expression of IL-10 in brain was higher in experimental group compared to those in the control group（P ＜0.05）, and the mRNA expression of TNF-α of experimental group was lower than that in the control group（P ＜0.05）. Conclusion The lymphocytes co-cultured with CB-SCs have immunotherapeutic effect on AD model mice, which is mainly displayed with increasing proportion of Tregs and enhanced anti-inflammatory function of Tregs．

Key words: Alzheimer’s Disease（AD）, cord blood-derived multipotent stem cells（CB-SCs）, lymphocytes, immune modulation