Abstract: Some years ago, the infiltration of T-cells into the central nervous system (CNS) was considered a pathological condition exclusively. However, during the last two decades, a growing body of studies has shown that T-cells are essential players regulating several physiological processes exerted by the CNS, including stress resilience, social behavior, anxiety, learning, and memory. Notably, the discovery of the meningeal lymphatics (Louveau et al., 2015) provided critical anatomical clues to a better understanding of the mechanisms by which T-cells collaborate with the CNS in cognitive and psychological processes. For instance, a number of mouse strains devoid of functional T-cells present worst adaptation to stress than immunocompetent counterparts, and the adoptive transfer of T-cells isolated from stress-experienced mice improves the psychological ability to adapt to stress in non-experienced mice appropriately (Brachman et al., 2015). Moreover, it has been demonstrated that T-cells deficiency results in anti-social behavior. The mechanistic analysis provided evidence indicating that interferon-gamma produced by meningeal T-cells stimulates GABAergic neurons, triggering inhibitory circuits that prevent hyperexcitability in the prefrontal cortex, thus promoting social behavior (Filiano et al., 2016). In addition, it has been shown that, through the production of interleukin (IL)-17, meningeal γδT-cells might stimulate cortical glutamatergic neurons inducing anxiety-like behavior in mice (Alves de Lima et al., 2020). Furthermore, another set of studies has shown that T-cells, particularly those CD4+ T-cells producing IL-4 and IL-13, are required for the proper learning and acquisition of memory (Derecki et al., 2010; Brombacher et al., 2017).