Immunohistochemical analysis of the cellular infiltrate in multiple sclerosis lesions

Abstract

Immunohistochemical staining of 16 brains post mortem from patients with progressive multiple sclerosis and of two biopsy specimens from patients with acute demyelinating disease was performed using a panel of monoclonal antibodies reactive with T cells and T-cell subsets, B cells, and Ia (HLA-DR) antigens. Lymphocytic perivascular cuffs were most prominent at the edge of active plaques and were occasionally seen in areas with no evidence of demyelination or macrophage infiltration. Perivascular cuffs consisted predominantly of T cells and Ia+ cells, with many T8+ cells and variable numbers of T4+ cells. T8/T4 ratios in cuffs varied between 1:1 and 50:1. In normal-appearing white matter, cuffs were sparse and were predominantly T8+. The distribution of T cells in the parenchyma resembled that seen in perivascular cuffs, namely, predominantly T8+ cells and variable numbers of T4+ cells. Many Ia+ cells were present in active lesions, and the majority of these cells appeared, by histological criteria, to be macrophages. Tissue macrophages were also stained lightly by the anti-T4 antibody. No brain had more T4+ than T8+ cells, determined using both T4 and Leu3a monoclonal antibodies. B1+ cells were rare. These results suggest that the cellular infiltrate in multiple sclerosis consists predominantly of T cells and macrophages and that there is an overrepresentation of T8+ cells compared with T4+ cells.

Interleukin-17 Production in Central Nervous System-Infiltrating T Cells and Glial Cells Is Associated with Active Disease in Multiple Sclerosis

“…[25][26][27][28] This finding is confirmed in the present study. The relative proportions of CD8 ϩ and CD4 ϩ T cells differ between studies, some describing a predominance of CD8 ϩ T cells 25,27,28 and others of CD4 ϩ cells.…”

“…As in previous studies, [25][26][27][28] we found significantly higher densities of T cells especially within perivascular areas of acute lesions (Figure 3A) and active borders of chronic active lesions ( Figure 3C) (2631 Ϯ 521 cells/mm 2 ), but also within inactive lesions ( Figure 3G) and inactive areas of chronic active lesions ( Figure 3E) (1080 Ϯ 208 cells/mm 2 ), than in NAWM ( Figure 3I) and control tissue ( Figure 3K) (495 Ϯ 143 cells/mm 2 , P ϭ 0.01; summarized in Figure 4A). Consistent with this observation, we noted significantly higher densities of IL-17 ϩ T cells within acute lesions ( Figure 3B) and active borders of chronic active lesions ( Figure 3D) (1687 Ϯ 284 cells/mm 2 ) than in NAWM (Figure 3J) and control tissue ( Figure 3L) (333 Ϯ 105 cells/ …”

T Cell Apoptosis and Induction of Foxp3+ Regulatory T Cells Underlie the Therapeutic Efficacy of CD4 Blockade in Experimental Autoimmune Encephalomyelitis

“…The strongest association is conferred by the human leukocyte/Ag locus (8). The inflammatory response present within the demyelinating lesions mainly comprises CD4 and CD8 T cells as well as macrophages (9). The commonly held view is that this response is autoreactive, targeting CNS-derived Ags (10).…”

Myelin oligodendrocyte glycoprotein peptide-induced experimental allergic encephalomyelitis and T cell responses are unaffected by immunoproteasome deficiency

“…However, clinical studies have reported that anti-CD4 monoclonal antibody therapy in MS patients does not prevent disease (Lindsey et al, 1994;van Oosten et al, 1997). Hence, CD4 + T cells may play a regulatory or modulatory role in this disease, rather than being the principal culprits; and detailed analyses of T lymphocytes in MS, including examination of brain tissue specimens, has determined that the majority of T cells are CD8 + (Booss et al, 1983;Traugott et al, 1983;Hauser et al, 1986a;Hauser et al, 1986b;McCallum et al, 1987). CD8 + T cells are found in MS lesions in the form of clonal populations, consistent with their having been locally expanded in response to a specific antigen (Babbe et al, 2000;reviewed, Steinman, 2001;Neumann et al, 2002).…”