Low-dose gamma-irradiation promotes survival of injured neurons in the central nervous system via homeostasis-driven proliferation of T cells.
Protective autoimmunity was only recently recognized as a mechanism for attenuating the progression of neurodegeneration. Using a rat model of optic nerve crush or contusive spinal cord injury, and a mouse model of neurodegenerative conditions caused by injection of a toxic dose of intraocular glutamate, we show that a single low dose of whole-body or lymphoid-organ gamma-irradiation significantly improved the spontaneous recovery. Animals with severe immune deficiency or deprived of mature T cells were unable to benefit from this treatment, suggesting that the irradiation-induced neuroprotection is immune mediated. This suggestion received further support from the findings that irradiation was accompanied by an increased incidence of activated T cells in the lymphoid organs and peripheral blood and an increase in mRNA encoding for the pro-inflammatory cytokines interleukin-12 and interferon-gamma, and that after irradiation, passive transfer of a subpopulation of suppressive T cells (naturally occurring regulatory CD4(+)CD25(+) T cells) wiped out the irradiation-induced protection. These results suggest that homeostasis-driven proliferation of T cells, induced by a single low-dose irradiation, leads to boosting of T cell-mediated neuroprotection and can be utilized clinically to fight off neurodegeneration and the threat of other diseases in which defense against toxic self-compounds is needed.
Kipnis
Jonathan
J
Department of Neurobiology, The Weizmann Institute of Science, Rehovot, Israel.
Avidan
Hila
H
Markovich
Yifat
Y
Mizrahi
Tal
T
Hauben
Ehud
E
Prigozhina
Tatyana B
TB
Slavin
Shimon
S
Schwartz
Michal
M
D000818:Animals; D002455:Cell Division / Q000276:immunology / Q000528:radiation effects; D002470:Cell Survival / Q000276:immunology / Q000528:radiation effects; D002490:Central Nervous System / Q000276:immunology / Q000528:radiation effects; D004307:Dose-Response Relationship, Radiation; D005260:Female; D005720:Gamma Rays / Q000627:therapeutic use*; D006706:Homeostasis / Q000276:immunology / Q000528:radiation effects*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D016513:Mice, SCID; D009474:Neurons / Q000166:cytology / Q000276:immunology / Q000528:radiation effects*; D020221:Optic Nerve Injuries / Q000276:immunology / Q000628:therapy; D051381:Rats; D011917:Rats, Inbred Lew; D017207:Rats, Sprague-Dawley; D012165:Retinal Ganglion Cells / Q000166:cytology / Q000276:immunology / Q000528:radiation effects; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000528:radiation effects*