Entzündung und axonale Schädigung in Läsionen der Multiplen Sklerose

Abstract

During the last years, axonal damage in multiple sclerosis (MS) has received increasing attention. Though there is evidence for a pathogenic role of CD8+ T cells, such as oligoclonal expansion of CD8+ T cells in MS lesions and a statistically significant correlation of the number of CD8+ T cells in MS lesions with the extent of acute axonal damage, the exact mechanisms of acute axonal damage in MS remain unclear. Here, we present further evidence for the hypothesis that CD8+ T cells are involved in acute axonal damage in MS. Examining tissue from 20 biopsied MS patients, we found that close appositions of CD8+ T cells and acutely damaged, APP+ axons are remarkably frequent. In actively demyelinating lesions, 17% of all infiltrating CD8+ T cells showed a close contact to APP+ axons, compared to 4% in inactive lesions. 43% of all infiltrating T cells within actively demyelinating lesions were CD8+, compared to 32% in inactive lesions. In a small sample of cases, a remarkable portion of all CD8+ T cells contained granzyme B+ granules.Additionally, we found differences between lesions of the neuropathological subtypes I, II and III according to Lucchinetti, Brück and Lassmann. The extent of acute axonal damage in pattern II was smaller than that in other patterns, whereas a less intense macrophage infiltration was observed in pattern III cases compared to other patterns. In pattern I, a remarkable higher portion of all T cells showed close appositions to APP+ axons, compared to the other patterns. Thus, our data support the hypothesis that MS is possibly not a single entity, but may represent different entities with similar clinical presentation. In the viral encephalitis cases examined, we could show that low but substantial acute axonal damage is present at a level of about one tenth of that found in MS lesions.