Beta-Amyloid Peptides Enhance the Proliferative Response of Activated CD4+CD28+ Lymphocytes from Alzheimer Disease Patients and from Healthy Elderly

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 beta-amyloid (A beta)-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 beta-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 A beta 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 A beta 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 A beta peptides on the immune system of AD patients does not depend on the specific reactivity to A beta 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 A beta peptide-exposed T lymphocytes and affecting the immune system performance.