Emeritus Group Neuroimmunology

Presentation and recognition of local autoantigen determines severity of autoimmune disease

The severity of actively induced EAE depends both on the nature of the autoantigen, as well as on the genetic make-up of the host animal. The classical encephalitogen, MBP, induces severe monophasic EAE in Lewis rats, but is much less efficient in other strains, for example the BN rat. Conversely, MOG is highly encephalitogenic in DA rats, but ineffective in Lewis rats.
Using the ΔNFAT-GFP probe, we showed that the encephalitogenic potential of myelin autoreactive T cells directly correlates with their ability to recognize the specific myelin autoantigen presented by leptomeningeal APCs (1).

1.M. Pesic et al., J. Clin. Invest. 123, 1192 (2013).

Movie 1: Calcium signaling in encephalitogenic T cells during peak EAE. Fluorescence image (left) and the pseudocolor ratio image (right) with T cells encircled and the blood vessel walls retraced are shown. MOG specific T cells (green) blood vessel (red).

Movie 2: Diapedesis of TMBP-GFP cells.
Intravital imaging was performed on day 2.5 after transfer of TMBP-GFP cells. Blood vessels were highlighted with Texas-red conjugated dextran injected intravenously (red). 2D-projected (left) and 3D reconstructed (right) movies are shown. A TMBP-GFP cell (green) is located in the vessel at the starting time point. The cell vividly changed its shape and finally extravasated.

Movie 3: Calcium signals in T cells after antigen recognition.
TOVA-Twitch cells are migrating within a popliteal lymph node of a mouse, displaying random short calcium spikes. After addition of the cognate antigen of the T cells (OVA) by intravenous injection, the cells immediately show a swift rise in their intracellular calcium levels and along with this a strongly reduced velocity. Antigen presenting dendritic cells (red) were labeled using SNARF.

Movie 4: TMBP-NFAT-GFP cells translocate ΔNFAT-GFP from the cytosol to nucleus upon contact with a local APC.
Two SNARF-labeled TMBP-NFAT-GFP (red/green) cells becoming activated (translocation of ΔNFAT-GFP from the cytosol to the nucleus) upon contact with a local APC (cyan, speculated outline indicated by a dotted line). The closed arrowheads indicate the T cell/APC interactions leading to activation, and the open arrows indicate the cells of interest. Note that both cells are receiving an activation signal from the same APC. The top right inserts show the cell of interest at a higher magnification in the red and green channels only. The relative time after the start of acquisition is indicated. Scale bar: 10 µm.

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