INTERACTIONS OF THE ALZHEIMER BETA-AMYLOID FRAGMENT((25-35)) WITH PERIPHERAL-BLOOD DENDRITIC CELLS

We have previously demonstrated that soluble amyloid beta protein (A b eta) induces IL-2 receptor expression and proliferation in peripheral T cells from young and old healthy individuals, but not from patients with Alzheimer's disease (AD). It seemed of interest to examine how th e immune system would react upon stimulation with A beta in its aggreg ated form. It was the aim of this study to define interactions between the spontaneously aggregating A beta((25-35)) and antigen-presenting cells. Human dendritic cells (DC), propagated from the peripheral bloo d of young healthy individuals, were incubated with A beta((25-35)) an d its effects on DC survival, cytokine release, and surface marker exp ression were monitored. The question whether DC could present amyloid to T cells was also addressed. We demonstrated that A beta((25-35)) do es not induce DC apoptosis or necrosis. This was shown by electron mic roscopy as well as by nuclear staining with propidium iodide. Some pep tide aggregates were found in intracellular vacuoles of DC. This proce ss did not increase production of TNF alpha and did not change the sur face expression of CD18, CD11a or CD11b. A decreased surface expressio n of MHC class II molecules was, however, noted. DC pulsed with A beta aggregates were unable to stimulate T cells in an autologous cocultur e system. The results demonstrate that amyloid may escape immune recog nition by its failure to activate antigen-presenting cells and by inhi biting MHC class II surface expression. (C) 1997 Elsevier Science Irel and Ltd.