Quantitation of antigen-specific T-cell-induced demyelination in vitro.

To test the hypothesis that T lymphocytes sensitized to central nervous system (CNS) antigens may quantitatively induce more demyelination in neural tissue than T cells sensitized to non-CNS antigens, we established T cell lines specific for myelin basic protein (MBP) or the purified protein derivative (PPD) of M. tuberculosis. The potential of T cells to cause myelin pathology was determined by measuring the activity of the myelin-associated enzyme 2'-3'-cyclic nucleotide 3'-phosphodiesterase (CNPase) in organotypic cultures of syngeneic spinal cord after incubation with the T cell lines. The activity of CNPase in neural tissue has been shown to correlate positively with the amount and integrity of CNS myelin. Although both MBP- and PPD-specific T cells caused decreases in CNPase activity, the MBP line caused significantly greater and consistent changes. This finding indicates that T cell-mediated CNS demyelination may be comprised of CNS antigen-specific and CNS non-specific components, the former causing more pathology.