T Cell Response to Amyloid-β and to Mitochondrial Antigens in Alzheimer’s Disease

Abstract

Despite the vast amount of literature on non-specific immune mechanisms in Alzheimer’s disease (AD), little is known about the role of antigen-specific immune responses. We investigated T cell reactivity to fragment 1–42 of amyloid-β (Aβ) and to N-terminal peptides of human mitochondrial and control microbial proteins. Thirty subjects with a diagnosis of probable AD according to NINCDS-ADRDA criteria and 30 sex- and age-matched healthy controls were enrolled. T cell responses to Aβ fragment showed no significant differences between AD patients and controls. By contrast, the mean number of positive T cell responses to both human mitochondrial and microbial peptides was significantly decreased in AD patients compared to control subjects. No significant correlation was found between T cell responses and both the severity of cognitive impairment and duration of the disease. Our results suggest that antigen-specific immune responses are impaired in AD. Protective immune responses to harmful amyloidogenic substances may also be impaired, thus favoring their accumulation in the brain.

Altered plasma cytokine levels in Alzheimer's disease: Correlation with the disease progression

“…The lack of proliferative responsiveness to amyloid burden in severe-AD led to the hypothesis of a "T cell anergy" in this stage [41]. A generally decreased in vitro T-cell-activation to a number of stimuli in AD has been described, and other studies have shown imbalances of cellular immunity and immunoregulatory T cells and a reduced T cell response to various antigenic determinants suggesting a defect of the T-cell-mediated immunity in AD [42]. The attenuation of the immune response may be related to the cerebral pathology in AD in terms of deficient phagocytosis of amyloid proteins, which, in turn, can lead to immune-mediated tissue degeneration.…”

An Attenuated Immune Response Is Sufficient to Enhance Cognition in an Alzheimer's Disease Mouse Model Immunized with Amyloid-β Derivatives

“…Evidence suggests that this toxicity was related to the Th-1, cytotoxic T-cell response (Schenk, 2002), which may be elicited by both the full length A␤ and the QS-21 adjuvant that promotes a cell-mediated Th-1 immune response (Kensil et al, 1995). More recently, A␤-reactive T-cells have been detected in Alzheimer's patients and controls (Giubilei et al, 2003;Monsonego et al, 2003), and T-cell responses toward A␤ fragments have been modulated with amino acid substitutions (Monsonego et al, 2003), supporting our approach (Sigurdsson et al, 2001;Knudsen et al, 2003).…”

Immunotherapy for Conformational Diseases

“…A contrasting finding indicated that T-cell response to various antigens decreases with age [74]. Yet another study did not observe differences in T-cell responses to Aβ fragments between AD and controls, but showed that general T-cell reactivity was attenuated in AD patients relative to controls as measured by response to human mitochondrial and microbial peptides [75]. This particular finding suggests that if overall T-cell reactivity is reduced in AD, a similar T-cell response in AD and controls towards Aβ may indicate a stronger reactivity in AD in response to Aβ than to other stimulants, although T-cell response towards Aβ varied substantially between subjects in this report, which complicates interpretation.…”