What T-cell receptors can tell us about neurologic disease

Abstract

Chronic demyelinating polyradiculoneuropathy (CIDP) is an acquired, potentially crippling sensory-motor polyneuropathy of variable course.1 It is likely autoimmune because sural nerve histopathology reveals infiltrating CD68+ macrophages, endoneurial and epineurial CD3+ T cells with immunoglobulin G, immunoglobulin M, and complement deposits on myelin sheaths.1 Macrophages penetrate the basal lamina of Schwann cells and split myelin lamellae, a process referred to as “macrophage-mediated demyelination.” Nerve injury ensues due to a combination of antibody-, complement-, and macrophage-dependent demyelination. The majority of patients therefore respond to corticosteroids, plasmapheresis, or IV immunoglobulin (IVIg). The Immune Globulin IV CIDP Efficacy (ICE) study, the largest therapeutic trial in CIDP, convincingly demonstrated short- and long-term benefits of IVIg treatment.2 Response to plasmapheresis or IVIg is consistent with humoral and Fc receptor–mediated cellular effector mechanisms. In this issue of Neurology ®, Schneider-Hohendorf et al.3 present evidence that CD8+ cytotoxic T cells contribute to the pathogenesis of CIDP: nerve-infiltrating CD8+ T cells are clonally expanded, with expanded T-cell clones also detectable in blood. In one especially informative patient, expanded T-cell receptor (TCR) β-chain variable (TCRVβ) 5.1+ T cells were enriched in sural nerve compared to blood. To interpret and understand these results, one needs to consider the methodology used in the study. CD8+ (cytotoxic) T cells typically recognize a short …