Glutamate decarboxylase 65-reactive immune cells (GAD65-reactive immune cells)

GAD65-reactive immune cells are a specialized population of lymphocytes, primarily T-cells, that pathologically recognize the 65 kDa isoform of glutamate decarboxylase (GAD65) as an autoantigen. GAD65 is a critical enzyme involved in the synthesis of the inhibitory neurotransmitter GABA and is highly expressed in pancreatic beta cells and GABAergic neurons (UniProt P18088). In conditions such as Type 1 Diabetes (T1D), these autoreactive cells escape immune tolerance and orchestrate the destruction of insulin-producing cells, while in Stiff-Person Syndrome (SPS), they are associated with severe neurological impairment (NINDS, 2023). Therapeutic strategies targeting these cells, most notably the GAD-alum vaccine (Diamyd), aim to reprogram the immune system toward a tolerogenic state to preserve endogenous organ function. Monitoring the activity of these cells and their associated autoantibodies serves as a vital clinical tool for assessing disease progression and the efficacy of antigen-specific immunotherapies (Lernmark & Larsson, 2013, Journal of Internal Medicine).

Other names

GAD65-specific T-cellsGAD65-autoreactive T-lymphocytesGAD65-reactive lymphocytesGAD65-specific immune cells

Induction of antigen-specific immune tolerance, promotion of regulatory T-cell (Treg) activity, and reduction of pro-inflammatory Th1/Th17 responses against GAD65-expressing tissues (Ludvigsson et al., 2021, Diabetes Care).