Maladaptation to mental stress mitigated by the adaptive immune system via depletion of naturally occurring regulatory CD4+CD25+ cells.
Peripheral cellular immunity was recently shown to play a critical role in brain plasticity and performance. The antigenic specificity of the participating 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 adaptation (measured by the acoustic startle response and avoidance behavior) in mice after their exposure to predator 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 CD4+CD25+ regulatory T cells were found to suppress this endogenous anti-stress attribute. These findings 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 T cells.
Ministry of Health Mental Health Center Anxiety and Stress Research Unit, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheva, Israel.
Hagit
H
Cohen
Yaniv
Y
Ziv
Michal
M
Cardon
Zeev
Z
Kaplan
Michael A
MA
Matar
Yori
Y
Gidron
Michal
M
Schwartz
Jonathan
J
Kipnis
D000222:Adaptation, Physiological / Q000276:immunology*; D000223:Adaptation, Psychological / Q000502:physiology; D000818:Animals; D015551:Autoimmunity / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002490:Central Nervous System / Q000276:immunology; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000276:immunology; D007108:Immune Tolerance / Q000276:immunology*; D007111:Immunity, Cellular / Q000276:immunology*; D053645:Interleukin-2 Receptor alpha Subunit / Q000276:immunology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D016513:Mice, SCID; D008822:Mice, Transgenic; D004676:Myelin Basic Protein / Q000276:immunology; D009419:Nerve Tissue Proteins / Q000276:immunology; D013313:Stress Disorders, Post-Traumatic / Q000276:immunology / Q000503:physiopathology; D013315:Stress, Psychological / Q000276:immunology* / Q000503:physiopathology
D053645:Interleukin-2 Receptor alpha Subunit; D004676:Myelin Basic Protein; D009419:Nerve Tissue Proteins