Increased CD8+ T Cell Response to Epstein-Barr Virus Lytic Antigens in the Active Phase of Multiple Sclerosis
Figure 4
Immunohistochemical detection of BZLF-1 in the inflamed meninges of the MS brain.
(A) A prominent immune infiltrate comprising a perivascular B-cell-follicle-like structure is visualized with anti-CD20 antibody in the meninges lining a cerebral sulcus of a MS case. (B) Immunostaining for the EBV immediate early lytic protein BZLF-1 in a serial section reveals the presence of several BZLF-1+ cells at the periphery of the B-cell follicle. Ig+ cells are present in the same area (inset). (C, D) High magnification pictures of Ig+ plasmablasts/plasma cells (green) coexpressing BZLF1 (red); these groups of cells correspond to those shown in the top left and bottom right parts of panel B. (E) Expression of the EBV early lytic protein BRFR1 (red) in a substantial proportion of Ig+ (red) plasmablasts/plasma cells in the same area shown in panel B; double immunofluorescence staining for Ig and BFRF-1 was performed in a section adjacent to those stained in A and B. (F) Two BZLF-1+ cells in another part of the B-cell-rich infiltrate shown in panel A. Nuclei were stained with DAPI (blue) in panels B-F. (G-K) Other examples of BZLF-1+ cells at the border of a meningeal B-cell follicle (G, H) and in a diffuse meningeal infiltrate (I-K) from a different MS case. Arrows in G and I point to the nuclei that are immunoreactive for BZLF-1 in H and J, respectively. The inset in panel K shows an Ig+ cell (green) with a BZLF-1+ nucleus (red) at high magnification. Bars = 100 µm in A and inset in B; 50 µm in B; 20 µm in C, E, F, K and inset in E; 10 µm in D, G, H and inset in K.