Interactions of the Alzheimer beta amyloid fragment (25-35) with peripheral blood dendritic cells.
We have previously demonstrated that soluble amyloid beta protein (A beta) 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 the immune system would react upon stimulation with A beta in its aggregated 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 blood of young healthy individuals, were incubated with A beta (25-35) and its effects on DC survival, cytokine release, and surface marker expression were monitored. The question whether DC could present amyloid to T cells was also addressed. We demonstrated that A beta (25-35) does not induce DC apoptosis or necrosis. This was shown by electron microscopy as well as by nuclear staining with propidium iodide. Some peptide aggregates were found in intracellular vacuoles of DC. This process did not increase production of TNF alpha and did not change the surface expression of CD18, CD11a or CD11b. A decreased surface expression of MHC class II molecules was, however, noted. DC pulsed with A beta aggregates were unable to stimulate T cells in an autologous coculture system. The results demonstrate that amyloid may escape immune recognition by its failure to activate antigen-presenting cells and by inhibiting MHC class II surface expression.
Schmitt
T L
TL
Institute for Biomedical Aging Research of the Austrian Academy of Sciences, Innsbruck, Austria.
Steger
M M
MM
Pavelka
M
M
Grubeck-Loebenstein
B
B
D000328:Adult; D000544:Alzheimer Disease / Q000276:immunology*; D016229:Amyloid beta-Peptides / Q000276:immunology*; D016923:Cell Death; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology*; D004705:Endocytosis; D005260:Female; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008297:Male; D010446:Peptide Fragments / Q000276:immunology*
D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; C074636:amyloid beta-protein (25-35)