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.
A potential role for the PD1/PD-L1 pathway in the neuroinflammation of Alzheimer's disease / M. Saresella, E. Calabrese, I. Marventano, F. Piancone, A. Gatti, E. Farina, M. Alberoni, M. Clerici. - In: NEUROBIOLOGY OF AGING. - ISSN 0197-4580. - 33:3(2012 Mar), pp. 624.e11-624.e22.
|Titolo:||A potential role for the PD1/PD-L1 pathway in the neuroinflammation of Alzheimer's disease|
CLERICI, MARIO SALVATORE (Ultimo)
|Parole Chiave:||Alzheimer's disease ; inflammation ; immunology ; Interleukin-10 ; PD1 ; PD-L1 ; apoptosis|
|Settore Scientifico Disciplinare:||Settore MED/04 - Patologia Generale|
|Data di pubblicazione:||mar-2012|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1016/j.neurobiolaging.2011.03.004|
|Appare nelle tipologie:||01 - Articolo su periodico|