The causal interrelation of CNS degeneration and adaptive immunity is assumed as a critical pathogenic element influencing the clinical phenotype in neuroinflammatory as well as in neurodegenerative disorders. We have recently shown that primary oligodendrocytic damage (by overexpression of PLP) leads to a low-grade inflammatory reaction of high pathological impact in the CNS, potentially reflecting pathogenic principles in some forms of multiple sclerosis. As a completely novel finding, these reactions were mediated by CD8+ T cells whereas CD4+ cells were not necessary for the pathological effects of the immune system. In order to yield further insights into pathogenic relevance and nature of the adaptive immune response in myelin mutated mice (PLP transgenic mice), we here apply a detailed immunological characterization of systemic and CNS-specific CD8+ T cell responses in PLP transgenic mice and aged wild type mice. We provide evidence that T effector cells are surveying the CNS of PLP transgenic and wild-type mice. These cells accumulate with age and show a higher level of activation in PLP transgenic mice. Exclusively in PLP transgenic mice, T cells show clonal expansions, as demonstrated by T cell receptor CDR3-spectratype analysis. Although we could not find specific responses of CD8+ T cells against myelin-antigen-derived peptides, V-beta/J-beta similarities strongly suggest specificity against a common antigen. Our data suggest that a primary degenerative CNS disorder, exemplified by PLP-transgenic mice, can be associated with secondary expansions of pathogenically relevant CD8+ T cells in the CNS. These findings have implications for our understanding of the role of secondary adaptive immune reactions in the context of neurodegenerative and neuroinflammatory diseases.