<b><i>Background:</i></b> Others and we have shown that T cells have an important role in hippocampal synaptic plasticity, including neurogenesis in the dentate gyrus, spinogenesis, and glutamatergic synaptic function in the CA of the hippocampus. Hippocampus plasticity is particularly involved in the brain effects of the enriched environment (EE), and interestingly CD4⁺ and CD8⁺ T cells play essential and differential roles in these effects. However, the precise mechanisms by which they act on the brain remain elusive. <b><i>Objectives:</i></b> We searched for a putative mechanism of action by which CD4⁺ T cells could influence brain plasticity and hypothesized that they could regulate protein transport at the level of the blood-CSF barrier in the choroid plexus. <b><i>Method:</i></b> We compared mice housed in EE and deprived of CD4⁺ T cells using a depleting antibody with a control group injected with the control isotype. We analyzed in the hippocampus the gene expression profiles using the Agilent system, and the expression of target proteins in plasma, CSF, and the choroid plexus using ELISA. <b><i>Results:</i></b> We show that CD4⁺ T cells may influence EE-induced hippocampus plasticity via thyroid hormone signaling by regulating in the choroid plexus the expression of transthyretin, the major transporter of thyroxine (T₄) to the brain parenchyma. <b><i>Conclusions:</i></b> Our study highlights the contribution of close interactions between the immune and neuroendocrine systems in brain plasticity and function.