Transition from enhanced T cell infiltration to inflammation in the myelin-degenerative central nervous system

Abstract

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 TH1/TC1 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.

Keywords

• CDR3 spectratyping
• T cells
• Myelin degeneration
• Inflammation
• Motility
• Microglia