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2-[18F]Fluoro-2-deoxy-ᴅ-glucose positron emission tomography ([18F]FDG PET) detection of the up-regulated glycolysis associated with malignant transformation is a noninvasive imaging technique used extensively in cancer diagnosis. Although striking similarities exist in glucose transport and metabolism between tumor cells and activated immune cells, the potential use of [18F]FDG PET for the diagnosis and evaluation of autoimmune disorders has not been systematically investigated. Here we ask whether [18F]FDG PET in conjunction with computed tomography (CT) could be used to monitor a complex autoimmune disorder such as murine experimental autoimmune encephalomyelitis (EAE) and whether this approach is sensitive enough to evaluate therapeutic interventions. We found that (i) coregistration of metabolic (i.e., microPET) and high-resolution anatomical (i.e., CT) images allows serial quantification of glycolysis with [18F]FDG in various spinal column segments; (ii) [18F]FDG PET/CT can detect the increased glycolysis associated with paralysis-causing inflammatory infiltrates in the spinal cord; and (iii) the [18F]FDG measure of glycolysis in the spinal cord is sensitive to systemic immunosuppressive therapy. These results highlight the potential use of serial [18F]FDG PET/CT imaging to monitor neuroinflammation in EAE and suggest that similar approaches could be applied to the diagnosis and evaluation of other autoimmune and inflammatory disorders in animal models and in humans. [ABSTRACT FROM AUTHOR]

Examines the kinetics and thermodynamics of T cell receptor (TCR)-autoantigen interactions in the autoimmune encephalomyelitis. Biophysical nature of T cell receptor-peptide MHC (pMHC) interactions; Binding of 172.1 TCR and myelin basic protein; Correlation between strength and plasticity of TCR-pMHC interaction.

Multiple sclerosis (MS) is an autoimmune disease driven by lymphocyte activation against myelin autoantigens in the central nervous system leading to demyelination and neurodegeneration. The deoxyribonucleoside salvage pathway with the rate‐limiting enzyme deoxycytidine kinase (dCK) captures extracellular deoxyribonucleosides for use in intracellular deoxyribonucleotide metabolism. Previous studies have shown that deoxyribonucleoside salvage activity is enriched in lymphocytes and required for early lymphocyte development. However, specific roles for the deoxyribonucleoside salvage pathway and dCK in autoimmune diseases such as MS are unknown. Here we demonstrate that dCK activity is necessary for the development of clinical symptoms in the MOG35–55 and MOG1–125 experimental autoimmune encephalomyelitis (EAE) mouse models of MS. During EAE disease, deoxyribonucleoside salvage activity is elevated in the spleen and lymph nodes. Targeting dCK with the small molecule dCK inhibitor TRE‐515 limits disease severity when treatments are started at disease induction or when symptoms first appear. EAE mice treated with TRE‐515 have significantly fewer infiltrating leukocytes in the spinal cord, and TRE‐515 blocks activation‐induced B and T cell proliferation and MOG35–55‐specific T cell expansion without affecting innate immune cells or naïve T and B cell populations. Our results demonstrate that targeting dCK limits symptoms in EAE mice and suggest that dCK activity is required for MOG35–55‐specific lymphocyte activation‐induced proliferation. [ABSTRACT FROM AUTHOR]