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Brain. 2017 Jan;140(1):184-200. doi: 10.1093/brain/aww270. Epub 2016 Nov 5.

Hippocampal T cell infiltration promotes neuroinflammation and cognitive decline in a mouse model of tauopathy.

Author information

1
1 Univ. Lille, Inserm, CHU-Lille, UMR-S 1172, Alzheimer and Tauopathies, Lille, France.
2
2 INSERM, UMRS 938, CdR Saint-Antoine, Laboratory Immune System, Neuroinflammation and Neurodegenerative Diseases, Hôpital St-Antoine, Paris, France.
3
3 Sorbonne Universités, UPMC Univ Paris 06, UMRS 938, CdR Saint-Antoine, Hôpital Saint-Antoine, Paris, France.
4
4 Inserm, U 1127, F-75013, Paris, France.
5
5 CNRS, UMR 7225, F-75013, Paris, France.
6
6 Sorbonne Universités, UPMC Univ Paris 06, UMR S 1127, F-75013, Paris, France.
7
7 Institut du Cerveau et de la Moelle épinière, ICM, F-75013, Paris, France.
8
8 BioImaging center of Lille, 59045 Lille, France.
9
9 Laboratoire de Neuropathologie Escourolle, Hôpital de la Salpêtrière, AP-HP, Paris, France.
10
1 Univ. Lille, Inserm, CHU-Lille, UMR-S 1172, Alzheimer and Tauopathies, Lille, France david.blum@inserm.fr.

Abstract

Alzheimer's disease is characterized by the combined presence of amyloid plaques and tau pathology, the latter being correlated with the progression of clinical symptoms. Neuroinflammatory changes are thought to be major contributors to Alzheimer's disease pathophysiology, even if their precise role still remains largely debated. Notably, to what extent immune responses contribute to cognitive impairments promoted by tau pathology remains poorly understood. To address this question, we took advantage of the THY-Tau22 mouse model that progressively develops hippocampal tau pathology paralleling cognitive deficits and reappraised the interrelationship between tau pathology and brain immune responses. In addition to conventional astroglial and microglial responses, we identified a CD8-positive T cell infiltration in the hippocampus of tau transgenic mice associated with an early chemokine response, notably involving CCL3. Interestingly, CD8-positive lymphocyte infiltration was also observed in the cortex of patients exhibiting frontemporal dementia with P301L tau mutation. To gain insights into the functional involvement of T cell infiltration in the pathophysiological development of tauopathy in THY-Tau22 mice, we chronically depleted T cells using anti-CD3 antibody. Such anti-CD3 treatment prevented hippocampal T cell infiltration in tau transgenic animals and reverted spatial memory deficits, in absence of tau pathology modulation. Altogether, these data support an instrumental role of hippocampal T cell infiltration in tau-driven pathophysiology and cognitive impairments in Alzheimer's disease and other tauopathies.

KEYWORDS:

T cells; chemokines; frontotemporal lobar degeneration; neuroinflammation; tauopathy

PMID:
27818384
PMCID:
PMC5382942
DOI:
10.1093/brain/aww270
[Indexed for MEDLINE]
Free PMC Article

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