Extended Data Fig. 9: The leptomeninges but not the dura are affected in chronic brain autoimmunity.
From: Distinct roles of the meningeal layers in CNS autoimmunity
a, Experimental set-up. Single or repeated inflammatory bouts were induced in tg-bSYN rats by 1- or 4-time transfer of TbSYN cells. Animals injected 1 or 4 times with TOVA cells were used as control. Analysis was performed 3 months upon the 1st or 4th bout. Clinical score (bars) and body weight change (lines). b, CNS inflammation persists in the leptomeninges but not in the dura after one inflammatory attack. Experimental set-up as in a. Infiltration pattern of CD43+ T cells and CD68+ myeloid cells in the leptomeninges (left panel) and dura (hemispheres and areas around the SSS, right panel) after single T cell transfer. Overviews images and magnified areas. Fluorescence microscopy. Green: Iba1+ microglia. SSS: superior sagittal sinus c, MHC class II is over-expressed in the leptomeninges upon a single inflammatory bout and it further increases upon repeated bouts. Overview pictures and magnified areas of the leptomeninges 3 months after 1x or 4x transfer of TOVA or TbSYN cells. Green: Iba1+ microglia. d, Repeated inflammatory bouts do not affect the dura at an ultrastructural level. Representative scanning micrographs of the dura after 4x transfer of TbSYN or TOVA cells. In the control (4x TOVA), to be seen is the neuroepithelium consisting of flat regular cells and the deeper extracellular layer identified as collagen bundles following the same direction (top). The other image of the same animal shows the superficial layer of thinner collagen fibers that are interlaced, forming the typical disorganized network. Similar findings are seen in the 4x TbSYN cell injected animal with no signs of destruction of the neuroepithelium or changes of the extracellular network. e, No spontaneous antigen presentation in the dura in chronic autoimmunity. IFNγ production from TbSYN cells cultured for 48 hours with APCs isolated from the indicated compartments in presence of cognate antigen 3 months after the 4th inflammatory bout. As control, an irrelevant antigen (OVA) or no antigen (NA) were added to the culture (values pooled together). ELISA. Each value represents a pool of 3 animals. Representative data of 2 independent experiments.
