The interaction between PD1 on T lymphocytes and PD-L1 on antigen presenting cells (APC) modulates the balance between inflammation and tolerance by inducing IL-10 production and apoptosis of antigen-specific cells. We analyzed the PD1/PD-L1 pathway, annexin V (AV)-expression, and proliferation in amyloid-beta (Aβ)-stimulated PBMC of patients with Alzheimer's disease (AD) (N = 35) or mild cognitive impairment (MCI) (N = 30) and of age-matched healthy controls (HC; N = 30). Results showed that PD1-expressing CD4 + T cells, density of PD-L1 on CD14 + APC, IL-10 production, and PD-L1-expressing/IL-10-producing CD14 + APC were significantly reduced in AD and MCI patients compared to HC. Aβ-stimulated PD1/AV-expressing (apoptotic) CD4 + T cells were also diminished, whereas proliferation was augmented in AD and MCI patients compared to controls. Finally, incubation of cells with PD-L1-neutralizing antibodies significantly decreased apoptosis of Aβ-specific CD4 + T lymphocytes. An impairment of the PD-L1/PD1 pathway is present in AD and MCI. Such alteration results in reduced IL-10 production and diminished apoptosis of Aβ-specific CD4 + T lymphocytes; these phenomena could play a role in the neuroinflammation accompanying AD.
|Journal||Neurobiology of Aging|
|Publication status||Published - Mar 2012|
- Alzheimer's disease
ASJC Scopus subject areas
- Clinical Neurology
- Developmental Biology
- Geriatrics and Gerontology