The ability to cope with ongoing neurodegeneration after injury to the central nervous system of mammals differs among strains and depends in part on the animal's ability to manifest a T-cell-mediated protective response. After CNS injury, strain-related differences were observed. Moreover, the post-injury effect of naturally occurring regulatory CD4+CD25+ T cells was found to differ in different strains. In this study, using partially injured optic nerves of Balb/c/OLA and C57BL/6J mice as models, we observed strain-related differences in the T-cell-mediated protection obtained by antigens administered via the nasal route. Active immunization with myelin-related antigens emulsified in complete Freund's adjuvant had a beneficial effect on both strains, whereas mucosal administration of the same antigens was destructive in mice of the Balb/c/OLA strain but protective in C57BL/6J mice.