T cell deficiency leads to cognitive dysfunction: implications for therapeutic vaccination for schizophrenia and other psychiatric conditions.
The effects of the adaptive immune system on the cognitive performance and abnormal behaviors seen in mental disorders such as schizophrenia have never been documented. Here, we show that mice deprived of mature T cells manifested cognitive deficits and behavioral abnormalities, which were remediable by T cell restoration. T cell-based vaccination, using glatiramer acetate (copolymer-1, a weak agonist of numerous self-reactive T cells), can overcome the behavioral and cognitive abnormalities that accompany neurotransmitter imbalance induced by (+)dizocilpine maleate (MK-801) or amphetamine. The results, by suggesting that peripheral T cell deficit can lead to cognitive and behavioral impairment, highlight the importance of properly functioning adaptive immunity in the maintenance of mental activity and in coping with conditions leading to cognitive deficits. These findings point to critical factors likely to contribute to age- and AIDS-related dementias and might herald the development of a therapeutic vaccination for fighting off cognitive dysfunction and psychiatric conditions.
Kipnis
Jonathan
J
Department of Neurobiology, Weizmann Institute of Science, 76100 Rehovot, Israel. jonathan.kipnis@weizmann.ac.il
Cohen
Hagit
H
Cardon
Michal
M
Ziv
Yaniv
Y
Schwartz
Michal
M
D000661:Amphetamine / Q000494:pharmacology; D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D003071:Cognition / Q000187:drug effects / Q000502:physiology; D003072:Cognition Disorders / Q000139:chemically induced / Q000276:immunology* / Q000503:physiopathology / Q000628:therapy*; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004797:Enzyme-Linked Immunosorbent Assay; D000068717:Glatiramer Acetate; D008297:Male; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D010455:Peptides / Q000008:administration & dosage / Q000276:immunology* / Q000494:pharmacology / Q000627:therapeutic use*; D013216:Reflex, Startle / Q000187:drug effects; D012559:Schizophrenia / Q000276:immunology* / Q000503:physiopathology / Q000628:therapy*; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D014611:Vaccination
D019208:Brain-Derived Neurotrophic Factor; D010455:Peptides; D000068717:Glatiramer Acetate; D016291:Dizocilpine Maleate; D000661:Amphetamine