Maladaptation to mental stress mitigated by the adaptive immune system via depletion of naturally occurring regulatory CD4+ CD25+ cells Academic Article uri icon


  • Peripheral cellular immunity was recently shown to play a critical role in brain plasticity and performance. The antigenic specificity of the partici- pating T cells, however, was not investigated, and nor was their relevance to psychological stress. Here we show, using a mouse model, that adaptive immunity mitigates maladaptation to the acute psychological stress known to trigger abnormal behaviors reminiscent of human post- traumatic stress disorder. Assessment of behavioral adap- tation (measured by the acoustic startle response and avoidance behavior) in mice after their exposure to preda- tor odor revealed that maladaptation was several times more prevalent in T cell-deficient mice than in their wild- type counterparts. A single population of T cells reactive to central nervous system (CNS)-associated self-protein was sufficient to endow immune-deficient mice with the ability to withstand the psychological stress. Naturally occurring CD4þCD25þ regulatory T cells were found to suppress this endogenous anti-stress attribute. These find- ings suggest that T cells specific to abundantly expressed CNS antigens are responsible for brain tissue homeostasis and help the individual to cope with stressful life episodes. They might also point the way to development of immune- based therapies for mental disorders, based either on up- regulation of T cells that partially cross-react with self- antigens or on weakening of the activity of regulatory Tc ells. ' 2006 Wiley Periodicals, Inc. J Neurobiol 66: 552-563, 2006

publication date

  • January 1, 2006