title: A potential role for the PD1/PD-L1 pathway in the neuroinflammation of Alzheimer's disease.
abstract: 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.
authors.affiliation: Laboratory of Molecular Medicine and Biotechnology, Don C. Gnocchi Foundation IRCCS, S. Maria Nascente, Milan, Italy. msaresella@dongnocchi.it
authors.forename: Marina
authors.initials: M
authors.lastname: Saresella
authors.forename: Elena
authors.initials: E
authors.lastname: Calabrese
authors.forename: Ivana
authors.initials: I
authors.lastname: Marventano
authors.forename: Federica
authors.initials: F
authors.lastname: Piancone
authors.forename: Andrea
authors.initials: A
authors.lastname: Gatti
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Farina
authors.forename: Margherita
authors.initials: M
authors.lastname: Alberoni
authors.forename: Mario
authors.initials: M
authors.lastname: Clerici
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology*; D016229:Amyloid beta-Peptides / Q000502:physiology; D060890:B7-H1 Antigen / Q000502:physiology*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009434:Neural Pathways / Q000473:pathology; D061026:Programmed Cell Death 1 Receptor / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*
chemical_list: D016229:Amyloid beta-Peptides; D060890:B7-H1 Antigen; C423236:CD274 protein, human; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor