Protective autoimmunity is a physiological response to CNS trauma

Primary damage caused by injury to the CNS is often followed by delayed deg eneration of initially spared neurons. Studies in our laboratory have shown that active or passive immunization with CNS myelin-associated self-antige ns can reduce this secondary loss. Here we show, using four experimental pa radigms in rodents, that CNS trauma spontaneously evokes a beneficial T cel l-dependent immune response, which reduces neuronal loss. (1) Survival of r etinal ganglion cells in rats was significantly higher when optic nerve inj ury was preceded by an unrelated CNS (spinal cord) injury. (2) Locomotor ac tivity of rat hindlimbs (measured in an open field using a locomotor rating scale) after contusive injury of the spinal cord (T8) was significantly be tter (by three to four score grades) after passive transfer of myelin basic protein (MBP)-activated splenocytes derived from spinally injured rats tha n in untreated injured control rats or rats similarly treated with splenocy tes from naive animals or with splenocytes from spinally injured rats activ ated 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 ma ture T cells (caused by thymectomy at birth) than in normal rats. (4) Retin al ganglion cell survival after optic nerve injury was higher (119 +/- 3.7% ) in transgenic mice overexpressing a T cell receptor (TcR) for MBP and low er (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 i mply that CNS injury evokes a T cell-dependent neuroprotective response.