Dendritic and Langerhans cells respond to Aβ peptides differently: implication for AD immunotherapy

Both wild-type and mutated beta-amyloid (Aβ) peptides can elicit an immune response when delivered subcutaneously. However, only mutated forms of Aβ can sensitize dendritic cells when administered intravenously or intraperitoneally. To understand the role of mutation and delivery routes in creating immune responses, and the function of dendritic cells as therapeutic agents, we used fluorescent-conjugated WT Aβ1-40 (WT40) and artificially mutated Aβ1-40 (22W40) peptides to treat dendritic and Langerhans cells from young and/or old mice at different time points. The cell types were analyzed by flow cytometry and confocal microscopy to identify differences in function and antigen presentation, and Luminex and Western blots for cell activation and associated mechanisms. Our results demonstrated that the artificial mutant, 22W40, enhanced dendritic cell's phagocytosis and antigen presentation better than the WT40. Interestingly, Langerhans cells were more effective at early presentation. The artificial mutant 22W40 increased CD8α(+) dendritic cells, CD8(+) T-cells, and IFN-γ production when co-cultured with self-lymphocytes and dendritic cells from aged mice (30-month-old). Here, the 22W40 mutant peptide has been found to be potent enough to activate DCs, and that dendritic cell-based therapy may be a more effective treatment for age-related diseases, such as Alzheimer's disease (AD).