Beta-Amyloid Peptides Enhance the Proliferative Response of Activated CD4+CD28+ Lymphocytes from Alzheimer Disease Patients and from Healthy Elderly
Open Access
- 12 March 2012
- journal article
- research article
- Published by Public Library of Science (PLoS) in PLOS ONE
- Vol. 7 (3), e33276
- https://doi.org/10.1371/journal.pone.0033276
Abstract
Alzheimer's disease (AD) is the most frequent form of dementia among elderly. Despite the vast amount of literature on non-specific immune mechanisms in AD there is still little information about the potential antigen-specific immune response in this pathology. It is known that early stages of AD include β-amyloid (Aβ)- reactive antibodies production and inflammatory response. Despite some evidence gathered proving cellular immune response background in AD pathology, the specific reactions of CD4+ and CD8+ cells remain unknown as the previous investigations yielded conflicting results. Here we investigated the CD4+CD28+ population of human peripheral blood T cells and showed that soluble β-amyloids alone were unable to stimulate these cells to proliferate significantly, resulting only in minor, probably antigen-specific, proliferative response. On the other hand, the exposure of in vitro pre-stimulated lymphocytes to soluble Aβ peptides significantly enhanced the proliferative response of these cells which had also lead to increased levels of TNF, IL-10 and IL-6. We also proved that Aβ peptide-enhanced proliferative response of CD4+CD28+ cells is autonomous and independent from disease status while being associated with the initial, ex vivo activation status of the CD4+ cells. In conclusion, we suggest that the effect of Aβ peptides on the immune system of AD patients does not depend on the specific reactivity to Aβ epitope(s), but is rather a consequence of an unspecific modulation of the cell cycle dynamics and cytokine production by T cells, occurring simultaneously in a huge proportion of Aβ peptide-exposed T lymphocytes and affecting the immune system performance.Keywords
This publication has 59 references indexed in Scilit:
- The Molecular Assembly of Amyloid Aβ Controls Its Neurotoxicity and Binding to Cellular ProteinsPLOS ONE, 2011
- Stoichiometry and Affinity of the Human Serum Albumin-Alzheimer's Aβ Peptide InteractionsBiophysical Journal, 2011
- The prion protein as a receptor for amyloid-βNature, 2010
- Toll‐like receptor 4 in CNS pathologiesJournal of Neurochemistry, 2010
- IFN-γ Promotes Complement Expression and Attenuates Amyloid Plaque Deposition in Amyloid β Precursor Protein Transgenic MicePublished by The American Association of Immunologists ,2010
- TLR4 signaling in effector CD4+ T cells regulates TCR activation and experimental colitis in miceJCI Insight, 2010
- Alzheimer's DiseaseNew England Journal of Medicine, 2010
- Human CD4low CD25high regulatory T cells indiscriminately kill autologous activated T cellsImmunology, 2009
- Cellular prion protein mediates impairment of synaptic plasticity by amyloid-β oligomersNature, 2009
- Immune response to Aβ-peptides in peripheral blood from patients with Alzheimer's disease and control subjectsNeuroscience Letters, 2004