title: Beta-amyloid peptides enhance the proliferative response of activated CD4CD28 lymphocytes from Alzheimer disease patients and from healthy elderly.
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.
authors.affiliation: Department of Pathophysiology, Medical University of Gdańsk, Gdańsk, Poland.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Jóźwik
authors.forename: Jerzy
authors.initials: J
authors.lastname: Landowski
authors.forename: Leszek
authors.initials: L
authors.lastname: Bidzan
authors.forename: Tamas
authors.initials: T
authors.lastname: Fülop
authors.forename: Ewa
authors.initials: E
authors.lastname: Bryl
authors.forename: Jacek M
authors.initials: JM
authors.lastname: Witkowski
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000276:immunology*; D016229:Amyloid beta-Peptides / Q000276:immunology* / Q000494:pharmacology; D018106:CD28 Antigens / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects*; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D016753:Interleukin-10 / Q000276:immunology; D015850:Interleukin-6 / Q000276:immunology; D008297:Male; D008875:Middle Aged; D018709:Statistics, Nonparametric; D048069:Tumor Necrosis Factors / Q000276:immunology
chemical_list: D016229:Amyloid beta-Peptides; D018106:CD28 Antigens; D015850:Interleukin-6; D048069:Tumor Necrosis Factors; D016753:Interleukin-10