CD4+ T cells and regulatory T cell functions in immunotherapy and in the pathophysiology of Alzheimer's disease : Studies in the mouse
type: Dataset
description: Cerebral accumulation of aggregated Aβ40-42 peptides is among the major pathological hallmarks of Alzheimer's disease (AD). In spite of encouraging results of Aβ vaccination in preclinical mouse models, the first human clinical trial had to be interrupted because of the occurence of meningoencephalitides in 6% of the cases, supposedly related to inappropriate T cell responses. Thus, a better understanding of vaccination-induced anti-Aβ CD4+ T cell responses seems essential for the optimisation of future immunotherapeutical approaches. We tried to identify the genetic factors that control the magnitude and the nature of vaccination-induced Aβ-specific CD4+ T cell responses in mice. Both MHC-dependent and MHC-independent genetic factors are critical parameters. Among MHC-independent genetic factors, those that determine the individual propensity of generating Aβ-specific regulatory T cell (Treg) responses are important. Moreover, the vaccination-induced CD4+ T cell responses analysis in an APPPS1 mouse model of AD suggest that Tregs may inhibit anti-Aβ CD4+ T cells responses that spontaneously arise in the course of AD. These observations led us to evaluate the impact of CD4+ effector and regulatory T cell responses in the pathophysiology of AD. Using Treg depletion experiments, we evidenced the anti-neuroinflammatory functions and beneficial effects of these cells on the amyloid pathology and cognition of APPPS1 mice. Altogether, our results suggest that Treg responses may both limit vaccination efficacy and have a neuroprotective role in the course of AD.
identifier: NNT: 2012PA066126
issued: 2026-05-10T13:11:48.444178
language: fr
modified: 2026-05-10T13:11:48.444183
contact point: Organization
  fn: CCSD
keyword: alzheimers-disease
keyword: cd4-t-cells
keyword: immunotherapie
keyword: immunotherapy
keyword: infoeu-reposemanticsdoctoralthesis
keyword: lymphocytes-t-cd4
keyword: lymphocytes-t-regulateurs
keyword: maladie-dalzheimer
keyword: neuroimmunologie
keyword: neuroimmunology
keyword: neuroinflammation
keyword: regulatory-t-cells
keyword: sdvimmlife-sciences-q-bioimmunology
keyword: theses
landing page: https://theses.hal.science/tel-00839313

CD4+ T cells and regulatory T cell functions in immunotherapy and in the pathophysiology of Alzheimer's disease : Studies in the mouse
type: Distribution
format: HTML
issued: 2026-05-10T13:11:48.448493
modified: 2026-05-10T13:11:48.431012
access URL: https://theses.hal.science/tel-00839313

test_moissonnage_selune
type: Agent