Myelin degeneration in the central nervous system (CNS) is often associated with elevated numbers of T cells in brain and spinal cord (SC). In some degenerative diseases, this T cell immigration has no clinical relevance, in others, it may precede severe inflammation and tissue damage. We studied T cells in the myelin-degenerative SC of transgenic (tg) Lewis rats overexpressing the proteolipid protein (PLP). These lymphocytes are T(H)1/T(C)1 cells and represent different T cell clones unique to individual animals. The SC-infiltrating CD8(+) T cell pool is more restricted than its CD4(+) counterpart, possibly due to constrictions in the peripheral CD8(+) T cell repertoire. Some SC-infiltrating T cells are highly motile and cover large distances within their target tissue, others are tethered to MHC class II(+) microglia cells. The activation of the tethered cells may trigger the formation of inflammatory foci and could pave the way for inflammation in degenerative CNS disease.