Th1 responses to beta-amyloid in young humans convert to regulatory IL-10 responses in Down syndrome and Alzheimer's disease.
A beta(1-42)-specific antibodies and T-cell proliferation point to the existence of a memory response to A beta(1-42) in humans. Using ELISPOT, we studied A beta(1-42)-specific T cells in individuals of various ages, and in subjects with Trisomy 21 or Alzheimer's disease. We show for the first time that A beta(1-42)-specific Th1-type T-cell memory is present in young humans, producing high levels of IFN-gamma and IL-2. With increasing age, the production of IFN-gamma and IL-2 decreases but is not discontinued in healthy subjects and is accompanied by a sharp rise in CD4(+) T-cell-derived regulatory IL-10 production. In contrast, individuals with Trisomy 21 and with Alzheimer's disease produce IL-10 only in the absence of any effector cytokine. This signifies a switch from a Th1 effector to an IL-10 mediated regulatory response.
Loewenbrueck
Kai F
KF
Department of Pathology, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA. kai.loewenbrueck@neuro.med.tu-dresden.de
Tigno-Aranjuez
Justine T
JT
Boehm
Bernhard O
BO
Lehmann
Paul V
PV
Tary-Lehmann
Magdalena
M
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000276:immunology*; D016229:Amyloid beta-Peptides / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D004314:Down Syndrome / Q000276:immunology*; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology / Q000378:metabolism; D016753:Interleukin-10 / Q000276:immunology*; D007376:Interleukin-2 / Q000276:immunology / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000378:metabolism; D010446:Peptide Fragments / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology*; D055815:Young Adult
D016229:Amyloid beta-Peptides; D007376:Interleukin-2; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); D016753:Interleukin-10; D007371:Interferon-gamma