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The Journal of Neuroscience, June 1, 2001, 21(11):3740-3748

Protective Autoimmunity Is a Physiological Response to CNS Trauma

Eti Yoles¹, Ehud Hauben¹, Orna Palgi³, Evgenia Agranov¹, Amalia Gothilf¹, Avi Cohen³, Vijay Kuchroo⁴, Irun R. Cohen², Howard Weiner⁴, and Michal Schwartz¹

Departments of ¹ Neurobiology and ² Immunology, The Weizmann Institute of Science, 76100 Rehovot, Israel, ³ Proneuron Ltd., Industrial Park, Ness-Ziona, Israel, and ⁴ Center for Neurologic Diseases, Harvard Medical School, Brigham and Women's Hospital, Boston, Massachusetts 02115

Primary damage caused by injury to the CNS is often followed by delayed degeneration of initially spared neurons. Studies in our laboratory have shown that active or passive immunization with CNS myelin-associated self-antigens can reduce this secondary loss. Here we show, using four experimental paradigms in rodents, that CNS trauma spontaneously evokes a beneficial T cell-dependent immune response, which reduces neuronal loss. (1) Survival of retinal ganglion cells in rats was significantly higher when optic nerve injury was preceded by an unrelated CNS (spinal cord) injury. (2) Locomotor activity of rat hindlimbs (measured in an open field using a locomotor rating scale) after contusive injury of the spinal cord (T8) was significantly better (by three to four score grades) after passive transfer of myelin basic protein (MBP)-activated splenocytes derived from spinally injured rats than in untreated injured control rats or rats similarly treated with splenocytes from naive animals or with splenocytes from spinally injured rats activated ex vivo with ovalbumin or without any ex vivo activation. (3) Neuronal survival after optic nerve injury was 40% lower in adult rats devoid of mature T cells (caused by thymectomy at birth) than in normal rats. (4) Retinal ganglion cell survival after optic nerve injury was higher (119 ± 3.7%) in transgenic mice overexpressing a T cell receptor (TcR) for MBP and lower (85 ± 1.3%) in mice overexpressing a T cell receptor for the non-self antigen ovalbumin than in matched wild types. Taken together, the results imply that CNS injury evokes a T cell-dependent neuroprotective response.

Key words: protective autoimmunity; CNS injury; spinal cord injury; optic nerve injury; neuroprotection; degeneration; encephalitogenic T cells

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Copyright © 2001 Society for Neuroscience  0270-6474/01/21113740-09$05.00/0

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