Evidence of a pathogenic role for CD8+ T cells in anti-GABAB receptor limbic encephalitis

Objectives: To characterize the cellular autoimmune response in patients with γ-aminobutyric acid (GABA) B receptor antibody–associated limbic encephalitis (GABA B -R LE). Methods: Patients underwent MRI, extensive neuropsychological assessment, and multiparameter flow cytometry of peripheral blood and CSF. Results: We identified a series of 3 cases of nonparaneoplastic GABA B -R LE and one case of paraneoplastic GABA B -R LE associated with small cell lung cancer. All patients exhibited temporal lobe epilepsy, neuropsychological deficits, and MRI findings typical of LE. Absolute numbers of CD19 + B cells, CD138 + CD19 + plasma cells, CD4 + T cells, activated HLADR + CD4 + T cells, as well as CD8 + T cells and HLADR + CD8 + T cells did not differ in peripheral blood but were elevated in CSF of patients with GABA B -R LE compared to controls. Augmented absolute numbers of CD138 + CD19 + plasma cells and activated HLADR + CD8 + T cells in CSF corresponded to higher overall neuropsychological and memory deficits in patients with GABA B -R LE. A histologic specimen of one patient following selective amygdalohippocampectomy revealed perivascular infiltrates of CD138 + plasma cells and CD4 + T cells, whereas cytotoxic CD8 + T cells were detected within the brain parenchyma in close contact to neurons. Conclusion: Our data suggest a pathogenic role for CD8 + T cells in addition to the established role of plasma cell–derived autoantibodies in GABA B -R LE.