Autoimmune diseases linked to abnormal K+ channel expression in double‐negative CD4CD8 T cells

Abstract
Using the patch‐clamp technique in combination with fluorescence microscopy we have found an abnormality in voltage‐gated K+ channel expression in T cells that represents the first molecular marker linking three disparate autoimmune diseases in mice. CD4CD8Thy‐1.2+ (double‐negative or DN) lymphocytes from every known murine model for systemic lupus erythematosus, type‐1 diabetes mellitus and experimental allergic encephalomyelitis exhibit abnormally high numbers of an unusual K+ channel, termed type l compared to their phenotypic counterparts in normal mice. Other T cell subsets from these diseased mice retain their normal pattern of K+ channel expression. The unique K+ channel phenotype of DN T cells arises in parallel with the onset of autoimmunity. Although mitogen‐activated T cells and rapidly proliferating thymocytes exhibit large numbers of K+ channels, these channels are of an electrophysiologically distinct type called n. Thus, abundant expression of type l K+ channels appears to be a useful marker for DN T cells associated with autoimmunity and may provide a valuable tool for delineating the role of DN T cells in the pathogenesis of autoimmune diseases.