Low-dose γ-irradiation promotes survival of injured neurons in the central nervous system via homeostasis-driven proliferation of T cells

• Published in: The European journal of neuroscience 2004-03, Vol.19 (5), p.1191-1198
• Main Authors: Kipnis, Jonathan, Avidan, Hila, Markovich, Yifat, Mizrahi, Tal, Hauben, Ehud, Prigozhina, Tatyana B., Slavin, Shimon
• Format: Article
• Language: English
• Subjects: Animals; CD25; CD4; Cell Division - immunology; Cell Division - radiation effects; Cell Survival - immunology; Cell Survival - radiation effects; Central Nervous System - immunology; Central Nervous System - radiation effects; CNS injury; Dose-Response Relationship, Radiation; Female; Gamma Rays - therapeutic use; Homeostasis - immunology; Homeostasis - radiation effects; low dose irradiation; lymphopenia; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Mice, SCID; neurodegeneration; Neurons - cytology; Neurons - immunology; Neurons - radiation effects; Optic Nerve Injuries - immunology; Optic Nerve Injuries - therapy; Rats; Rats, Inbred Lew; Rats, Sprague-Dawley; Retinal Ganglion Cells - cytology; Retinal Ganglion Cells - immunology; Retinal Ganglion Cells - radiation effects; T cell-mediated neuroprotection; T-Lymphocytes - cytology; T-Lymphocytes - immunology; T-Lymphocytes - radiation effects
• ISSN: 0953-816X; 1460-9568
• DOI: 10.1111/j.1460-9568.2004.03207.x

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 γ‐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‐γ, 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.