Autoimmune diseases linked to abnormal K+ channel expression in double-negative CD4-CD8- T cells.
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. CD4-CD8-Thy-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.
Chandy
K G
KG
Department of Medicine, University of California, Irvine 92717.
Cahalan
M D
MD
Grissmer
S
S
D000818:Animals; D001327:Autoimmune Diseases / Q000209:etiology / Q000378:metabolism*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D002908:Chronic Disease; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000378:metabolism; D008180:Lupus Erythematosus, Systemic / Q000378:metabolism; D051379:Mice; D008815:Mice, Inbred Strains; D015221:Potassium Channels / Q000502:physiology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000378:metabolism*
D015221:Potassium Channels