Multiple sclerosis. Distribution of T cells, T cell subsets and Ia-positive macrophages in lesions of different ages

Abstract

Using monoclonal antibodies in combination with the PAP technique, total (T11+) T cells, helper-inducer (T4+) T cells, suppressor-cytotoxic (T8+) T cells and Ia+ cells (macrophages and B cells) were localized in frozen sections of multiple sclerosis (MS) lesions with varied disease activity. In acute MS, T11+, T4+, T8+ cells and Ia+ macrophages were found in large numbers throughout the lesion but were virtually absent from normal white matter. In active chronic MS lesions, the numbers of T11+, T4+ and T8+ cells increased from the center towards the edge of the lesion. T11+ and T4+ cells penetrated deeply into the normal-appearing white matter adjacent to the lesion, while T8+ cells were more confined to the lesion edge. Ia+ macrophages displayed a reverse distribution pattern to that of T cells. They showed the highest density in the lesion center and their numbers decreased slightly towards the lesion edge. Small numbers of T11+, T4+, T8+ and Ia+ cells were always present in normal white matter. In silent chronic MS lesions, the numbers of both T cells and Ia+ cells were significantly lower than in active chronic MS. While T11+ and T4+ cells were found throughout the central nervous system (CNS), T8+ cells were virtually absent from the lesion center. Ia+ macrophages were also present in small numbers throughout the CNS and, sometimes, showed some accumulation at the lesion edge. Thus, T cells and T cell subsets have been demonstrated to be involved in lesion pathogenesis in MS in that lesion progression was associated with T4+ cells while ongoing demyelination depended upon the presence of Ia+ macrophages.