Cytotoxic activity of peripheral blood and cerebrospinal fluid lymphocytes from patients with multiple sclerosis and other neurological diseases: analysis at the single cell level of the relationship of cytotoxic effectors and interferon-producing cells.

The production of interferon (IFN alpha) in relationship to NK and ADCC activity of peripheral blood and cerebrospinal lymphocytes was examined at the single cell level in patients with multiple sclerosis (MS) and other neurological diseases (OND) compared with age- and sex-matched controls. IFN-producing cells were assessed by indirect immunofluorescent scoring of cytoplasmic IFN+ cells. Peak production of cytoplasmic IFN alpha in nylon wool-passed ( NWP ) cells occurred between 5 and 17 hr in vitro under the inductive stimulus of MOLT 4, K562, or antibody-coated Chang liver cells. The proportion of K562- and MOLT 4-induced IFN alpha-positive cells in the total lymphocyte and target-binding cell (TBC) population was significantly lower in MS NWP -peripheral blood lymphocytes (PBL) than in OND and normal controls; this was in direct relationship to a decreased percentage of NK cells in MS PBL. In contrast MS cells responded the same as controls (total IFN+ cells) or higher than controls (IFN+-TBC) after IFN alpha induction by antibody-coated Chang, the ADCC target, in parallel with elevated ADCC activity by MS PBL. MS CSF contained a higher proportion of total IFN+ cells but a similar proportion of IFN+-TBC as their homologous NWP PBL population. In OND CSF, both the percentage of total IFN+ and the percentage of IFN+-TBC were higher than in OND blood and higher than their respective MS CSF populations. The relationship of IFN-producing cells in the central nervous system (CNS) to putative cytotoxic cells is discussed.