CD8 + T cells are essential for the effects of enriched environment on hippocampus-dependent behavior, hippocampal neurogenesis and synaptic plasticity

Hadi Zarif (1) , Sarah Nicolas (1) , Mélanie Guyot (2) , Salma Hosseiny (1) , Anne Lazzari (3) , María Magdalena Canali , Julie Cazareth (4) , Frédéric Brau (1) , Valentine Golzné (1) , Elisa Dourneau (1) , Maud Maillaut (1) , Carmelo Luci (5) , Agnès Paquet (1) , Kevin Lebrigand (1) , Marie-Jeanne Arguel (1) , Douglas Daoudlarian (1) , Catherine Heurteaux (1) , Nicolas Glaichenhaus (1) , Joëlle Chabry (1) , Alice Guyon (1) , Agnès Petit-Paitel (1)

1 IPMC - Institut de pharmacologie moléculaire et cellulaire
2 IRCAN - Institut de Recherche sur le Cancer et le Vieillissement
3 Immunologie des muqueuses et inflammation
4 UNS - Université Nice Sophia Antipolis (1965 - 2019)
5 Immunité muqueuse et vaccination

Enriched environment (EE) induces plasticity changes in the brain. Recently, CD4 + T cells have been shown to be involved in brain plasticity processes. Here, we show that CD8 + T cells are required for EE-induced brain plasticity in mice, as revealed by measurements of hippocampal volume, neurogenesis in the DG of the hippocampus, spinogenesis and glutamatergic synaptic function in the CA of the hip-pocampus. As a consequence, EE-induced behavioral benefits depend, at least in part, on CD8 + T cells. In addition, we show that spleen CD8 + T cells from mice housed in standard environment (SE) and EE have different properties in terms of 1) TNFa release after in vitro CD3/CD28 or PMA/Iono stimulation 2) in vitro proliferation properties 3) CD8 + CD44 + CD62L low and CD62L hi T cells repartition 4) transcrip-tomic signature as revealed by RNA sequencing. CD8 + T cells purified from the choroid plexus of SE and EE mice also exhibit different transcriptomic profiles as highlighted by single-cell mRNA sequencing. We show that CD8 + T cells are essential mediators of beneficial EE effects on brain plasticity and cogni-tion. Additionally, we propose that EE differentially primes CD8 + T cells leading to behavioral improvement.

Mots clés: mice, brain plasticity, hippocampus, CD4 + T cells, enriched environment

Domaines: Neurobiologie

Hadi Zarif, Sarah Nicolas, Mélanie Guyot, Salma Hosseiny, Anne Lazzari, et al.. CD8 + T cells are essential for the effects of enriched environment on hippocampus-dependent behavior, hippocampal neurogenesis and synaptic plasticity. Brain, Behavior, and Immunity, 2018, 69, pp.235-254. ⟨10.1016/j.bbi.2017.11.016⟩. ⟨hal-02269093⟩