CD4 T Cells Have a Permissive Effect on Enriched Environment-Induced Hippocampus Synaptic Plasticity
Authors: Marie-Jeanne Arguel
Agnès Petit-Paitel
Joëlle Chabry
Nicolas Glaichenhaus
Hadi Zarif
Anne Lazzari
Julie Cazareth
Salma Hosseiny
Catherine Heurteaux
Agnès Paquet
Kevin Lebrigand
Alice Guyon
Journal: Frontiers in Synaptic Neuroscience (2018)
Discipline: NEUROSCIENCE & BEHAVIOR
Keywords: CD4+ T cells; brain plasticity; enriched environment; hippocampus; mice.
Affiliations: Université Côte d'Azur, CNRS, IPMC, Nice, France., Université Côte d'Azur, INSERM, IPMC, Nice, France., Université Côte d'Azur, INSERM, C3M, IPMC, Nice, France.

Abstract:  Living in an enriched environment (EE) benefits health by acting synergistically on various biological systems including the immune and the central nervous systems. The dialog between the brain and the immune cells has recently gained interest and is thought to play a pivotal role in beneficial effects of EE. Recent studies show that T lymphocytes have an important role in hippocampal plasticity, learning, and memory, although the precise mechanisms by which they act on the brain remain elusive. Using a mouse model of EE, we show here that CD4+ T cells are essential for spinogenesis and glutamatergic synaptic function in the CA of the hippocampus. However, CD4+ lymphocytes do not influence EE-induced neurogenesis in the DG of the hippocampus, by contrast to what we previously demonstrated for CD8+ T cells. Importantly, CD4+ T cells located in the choroid plexus have a specific transcriptomic signature as a function of the living environment. Our study highlights the contribution of CD4+ T cells in the brain plasticity and function. 

Retracted: No

PubPeer comments:
 The job of CD4+ T cells is to recognize specific antigens by their T-cell receptor. How would that be related to the response of an animal to an enriched environment? Which is the mechanism suggested by the authors of this paper? Furthermore, it would have been interesting to see the effects of depletion of other myeloid populations in the same system. , 
 We have not yet fully elucidated the mechanism by which CD4+ T cells are influencing the hippocampal plasticity. We have shown that their depletion reduces plasticity elicited by enriched environment. During enriched environment, the CD4+ T cells adopt a new phenotype. They are present at the choroid plexus where they can exert an influence on cells lining the ventricles. By stimulating the TTR production, they would increase thyroid hormon transport to the brain, which are known to promote plasticity. We also investigated the effect of the depletion of CD8+ t cells and of CD25+ T cells among CD4+ T cells. The results are published in other published papers . CD4+ T Cells Have a Permissive Effect on Enriched Environment-Induced Hippocampus Synaptic Plasticity. Zarif H, Hosseiny S, Paquet A, Lebrigand K, Arguel MJ, Cazareth J, Lazzari A, Heurteaux C, Glaichenhaus N, Chabry J, Guyon A, Petit-Paitel A. Front Synaptic Neurosci. 2018 Jun 13;10:14. doi: 10.3389 fnsyn.2018.00014. eCollection 2018. CD8+ T cells are essential for the effects of enriched environment on hippocampus-dependent behavior, hippocampal neurogenesis and synaptic plasticity. Zarif H, Nicolas S, Guyot M, Hosseiny S, Lazzari A, Canali MM, Cazareth J, Brau F, Golznu00e9 V, Dourneau E, Maillaut M, Luci C, Paquet A, Lebrigand K, Arguel MJ, Daoudlarian D, Heurteaux C, Glaichenhaus N, Chabry J, Guyon A, Petit-Paitel A. Brain Behav Immun. 2018 Mar;69:235-254. doi: 10.1016 j.bbi.2017.11.016. Epub 2017 Nov 22. ,