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

Jonathan Kipnis, Hila Avidan, Yifat Markovich, Tal Mizrahi, Ehud Hauben, Tatyana B. Prigozhina, Shimon Slavin, Michal Schwartz

Research output: Contribution to journalArticlepeer-review

56 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)1191-1198
Number of pages8
JournalEuropean Journal of Neuroscience
Volume19
Issue number5
DOIs
StatePublished - Mar 2004

Keywords

  • CD25
  • CD4
  • CNS injury
  • Low dose irradiation
  • Lymphopenia
  • Neurodegeneration
  • T cell-mediated neuroprotection

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