- Trafficking of T lymphocytes to specific organs, such as the skin and lungs, is part of the body’s defense mechanism following acute psychological stress. Here we demonstrate that T lymphocytes are also trafficking to the brain in response to psychological stress and are needed to alleviate its negative behavioral consequences. We show that short exposure of mice to a stressor (predator odor) enhanced T-cell infiltration to the brain, especially to the choroid plexus, and that this infiltration was associated with increased ICAM-1 expression by choroid plexus cells. Systemic administration of corticosterone could mimic the effects of psychological stress on ICAM-1 expression. Furthermore, we found that the ability to cope with this stress is interrelated with T-cell trafficking and with the brain and hippocampal BDNF levels. Immunization with a CNS-related peptide reduced the stress-induced anxiety and the acoustic startle response, and restored levels of BDNF, shown to be important for stress resilience. These results identified T cells as novel players in coping with psychological stress, and offers immunization with a myelin-related peptide as a new therapeutic approach to alleviate chronic consequences of acute psychological trauma, such as those found in posttraumatic stress disorder.