A potential role for the PD1/PD-L1 pathway in the neuroinflammation of Alzheimer's disease

Marina Saresella, Elena Calabrese, Ivana Marventano, Federica Piancone, Andrea Gatti, Elisabetta Farina, Margherita Alberoni, Mario Clerici

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish
JournalNeurobiology of Aging
Issue number3
Publication statusPublished - Mar 2012


  • Alzheimer's disease
  • Apoptosis
  • Immunology
  • Inflammation
  • Interleukin-10
  • PD-L1
  • PD1

ASJC Scopus subject areas

  • Clinical Neurology
  • Neuroscience(all)
  • Ageing
  • Developmental Biology
  • Geriatrics and Gerontology


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