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Translational imaging of TSPO reveals pronounced innate inflammation in human and murine CD8 T cell-mediated limbic encephalitis

Gallus, M;Roll, W;Dik, A;Barca, C;Zinnhardt, B;Hicking, G;Mueller, C;Naik, VN;Anstötz, M;Krämer, J;Rolfes, L;Wachsmuth, L;Pitsch, J;van Loo, KMJ;Räuber, S;Okada, H;Wimberley, C;Strippel, C;Golombeck, KS;Johnen, A;Kovac, S;Groß, CC;Backhaus, P;Seifert, R;Lewerenz, J;Surges, R;Elger, CE;Wiendl, H;Ruck, T;Becker, AJ;Faber, C;Jacobs, AH;Bauer, J;Meuth, SG;Schäfers, M;Melzer, N;

Autoimmune limbic encephalitis (ALE) presents with new-onset mesial temporal lobe seizures, progressive memory disturbance, and other behavioral and cognitive changes. CD8 T cells are considered to play a key role in those cases where autoantibodies (ABs) target intracellular antigens or no ABs were found. Assessment of such patients presents a clinical challenge, and novel noninvasive imaging biomarkers are urgently needed. Here, we demonstrate that visualization of the translocator protein (TSPO) with [18F]DPA-714-PET-MRI reveals pronounced microglia activation and reactive gliosis in the hippocampus and amygdala of patients suspected with CD8 T cell ALE, which correlates with FLAIR-MRI and EEG alterations. Back-translation into a preclinical mouse model of neuronal antigen-specific CD8 T cell-mediated ALE allowed us to corroborate our preliminary clinical findings. These translational data underline the potential of [18F]DPA-714-PET-MRI as a clinical molecular imaging method for the direct assessment of innate immunity in CD8 T cell-mediated ALE.