Potassium Channels, Memory T Cells, and Multiple Sclerosis

Multiple sclerosis is a chronic inflammatory autoimmune disease of the central nervous system characterized by demyelination and axonal damage that result in disabling neurological deficits. Here the authors explain the rationale for the use of inhibitors of the Kv1.3 K+ channel in immune cells as a therapy for multiple sclerosis and other autoimmune disorders.

[1]  L. Schlichter,et al.  A Kv1.5 to Kv1.3 Switch in Endogenous Hippocampal Microglia and a Role in Proliferation , 1999, The Journal of Neuroscience.

[2]  D. Armstrong,et al.  Stimulation of Kv1.3 Potassium Channels by Death Receptors during Apoptosis in Jurkat T Lymphocytes* , 2003, Journal of Biological Chemistry.

[3]  C. Deutsch,et al.  K channels in T lymphocytes: a patch clamp study using monoclonal antibody adhesion , 1984, Nature.

[4]  F. Barkhof,et al.  Treatment with laquinimod reduces development of active MRI lesions in relapsing MS , 2005, Neurology.

[5]  E. Gallin.  Calcium- and voltage-activated potassium channels in human macrophages. , 1984, Biophysical journal.

[6]  K. Chandy,et al.  Two types of potassium channels in murine T lymphocytes , 1987, The Journal of general physiology.

[7]  Keli Xu,et al.  Calcium oscillations increase the efficiency and specificity of gene expression , 1998, Nature.

[8]  P. V. D. van de Kerkhof,et al.  Memory effector (CD45RO+) and cytotoxic (CD8+) T cells appear early in the margin zone of spreading psoriatic lesions in contrast to cells expressing natural killer receptors, which appear late , 2004, The British journal of dermatology.

[9]  R. V. van Vollenhoven,et al.  CD28nullCD4+ T Cells – Characterization of an Effector Memory T‐Cell Population in Patients with Rheumatoid Arthritis , 2004, Scandinavian journal of immunology.

[10]  R. Banati,et al.  Brain microglia and blood-derived macrophages: molecular profiles and functional roles in multiple sclerosis and animal models of autoimmune demyelinating disease , 2004, Brain Research Reviews.

[11]  E. Gulbins,et al.  Actinomycin D-induced apoptosis involves the potassium channel Kv1.3. , 2002, Biochemical and biophysical research communications.

[12]  M. D'hooghe,et al.  T‐cell reactivity to multiple myelin antigens in multiple sclerosis patients and healthy controls , 2001, Journal of neuroscience research.

[13]  A. Komiyama,et al.  CD27: a memory B-cell marker. , 2000, Immunology today.

[14]  H. Wulff,et al.  Design of PAP-1, a Selective Small Molecule Kv1.3 Blocker, for the Suppression of Effector Memory T Cells in Autoimmune Diseases , 2005, Molecular Pharmacology.

[15]  T. Kawai,et al.  Selective Blockade of Voltage‐Gated Potassium Channels Reduces Inflammatory Bone Resorption in Experimental Periodontal Disease , 2003, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[16]  M. Mańczak,et al.  Phenotypes of T cells infiltrating the eyes in autoimmune anterior uveitis associated with EAE. , 2002, Investigative ophthalmology & visual science.

[17]  P. Calabresi,et al.  Kv1.3-blocking 5-phenylalkoxypsoralens: a new class of immunomodulators. , 2004, Molecular pharmacology.

[18]  R. Davies,et al.  CD56bright NK Cells Are Enriched at Inflammatory Sites and Can Engage with Monocytes in a Reciprocal Program of Activation1 , 2004, The Journal of Immunology.

[19]  A. Ziegler,et al.  Oligoclonal expansion of memory CD8+ T cells in cerebrospinal fluid from multiple sclerosis patients. , 2002, Brain : a journal of neurology.

[20]  L. Kaczmarek,et al.  Compensatory Anion Currents in Kv1.3 Channel-deficient Thymocytes* , 2003, Journal of Biological Chemistry.

[21]  F. A. Davis,et al.  Orally administered 4‐aminopyridine improves clinical signs in multiple sclerosis , 1990, Annals of neurology.

[22]  M. Petrović,et al.  Hypoxia Regulates Expression and Activity of Kv1.3 Channels in T Lymphocytes: A Possible Role in T Cell Proliferation1 , 2003, The Journal of Immunology.

[23]  P. Lipsky,et al.  Diminished peripheral blood memory B cells and accumulation of memory B cells in the salivary glands of patients with Sjögren's syndrome. , 2002, Arthritis and rheumatism.

[24]  G. Wolswijk.  Oligodendrocyte survival, loss and birth in lesions of chronic-stage multiple sclerosis. , 2000, Brain : a journal of neurology.

[25]  C. Eder.  Ion channels in microglia (brain macrophages). , 1998, American journal of physiology. Cell physiology.

[26]  W. Waldhäusl,et al.  Elevated CD69 expression on naive peripheral blood T-cells in hyperthyroid Graves' disease and autoimmune thyroiditis: discordant effect of methimazole on HLA-DR and CD69. , 1998, Clinical immunology and immunopathology.

[27]  K. Chandy,et al.  Potassium channels as therapeutic targets for autoimmune disorders. , 2003, Current opinion in drug discovery & development.

[28]  P. Calabresi,et al.  Targeting Effector Memory T Cells with a Selective Peptide Inhibitor of Kv1.3 Channels for Therapy of Autoimmune Diseases , 2005, Molecular Pharmacology.

[29]  Bart O. Roep Dr..  The role of T-cells in the pathogenesis of Type 1 diabetes: From cause to cure , 2003, Diabetologia.

[30]  M. Cahalan,et al.  Subset-specific expression of potassium channels in developing murine T lymphocytes. , 1988, Science.

[31]  S. Hagiwara,et al.  Potassium channels mediate killing by human natural killer cells. , 1986, Proceedings of the National Academy of Sciences of the United States of America.

[32]  J. Burns,et al.  Isolation of myelin basic protein–specific T cells predominantly from the memory T‐cell compartment in multiple sclerosis , 1999, Annals of neurology.

[33]  F. Lang,et al.  A Novel Potassium Channel in Lymphocyte Mitochondria* , 2005, Journal of Biological Chemistry.

[34]  K. Asadullah,et al.  Flow cytometric characterization of lesional T cells in psoriasis: intracellular cytokine and surface antigen expression indicates an activated, memory/effector type 1 immunophenotype , 2000, Archives of Dermatological Research.

[35]  L. Bekar,et al.  Ion channels in cultured microglia , 2001, Microscopy research and technique.

[36]  Antonio Lanzavecchia,et al.  Central memory and effector memory T cell subsets: function, generation, and maintenance. , 2004, Annual review of immunology.

[37]  Bart O. Roep,et al.  The role of T-cells in the pathogenesis of Type 1 diabetes: From cause to cure , 2003, Diabetologia.

[38]  K. Chandy,et al.  Molecular Properties and Physiological Roles of Ion Channels in the Immune System , 2001, Journal of Clinical Immunology.

[39]  K. Chandy,et al.  Voltage-gated K+ channels in human T lymphocytes: a role in mitogenesis? , 1984, Nature.

[40]  X. Zhu,et al.  K+ channels and the microglial respiratory burst. , 2001, American journal of physiology. Cell physiology.

[41]  G. Krueger,et al.  Treatment of chronic plaque psoriasis by selective targeting of memory effector T lymphocytes. , 2001, The New England journal of medicine.

[42]  C. Schauf,et al.  4‐Aminopyridine improves clinical signs in multiple sclerosis , 1987, Annals of neurology.

[43]  S. Hagiwara,et al.  Potassium current in clonal cytotoxic T lymphocytes from the mouse. , 1984, The Journal of physiology.

[44]  A. Celada,et al.  Differential Voltage-dependent K+ Channel Responses during Proliferation and Activation in Macrophages* , 2003, Journal of Biological Chemistry.

[45]  A. Evans,et al.  Induction of a non-encephalitogenic type 2 T helper-cell autoimmune response in multiple sclerosis after administration of an altered peptide ligand in a placebo-controlled, randomized phase II trial , 2000, Nature Medicine.

[46]  T. Heckman,et al.  Regulation of Kv1 subunit expression in oligodendrocyte progenitor cells and their role in G1/S phase progression of the cell cycle , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[47]  A. Schwab,et al.  Functional importance of Ca2+‐activated K+ channels for lysophosphatidic acid‐induced microglial migration , 2004, The European journal of neuroscience.

[48]  H. Vijverberg,et al.  Intracellular Ca2+ oscillations and membrane potential fluctuations in intact human T lymphocytes: role of K+ channels in Ca2+ signaling. , 1995, Cell calcium.

[49]  T. Chused,et al.  Lack of voltage sensitive potassium channels and generation of membrane potential by sodium potassium ATPase in murine T lymphocytes. , 1993, Journal of immunology.

[50]  A. Weinberg,et al.  Transforming growth factor-beta enhances the in vivo effector function and memory phenotype of antigen-specific T helper cells in experimental autoimmune encephalomyelitis. , 1992, Journal of immunology.

[51]  D. Clapham,et al.  Development of a delayed outward-rectifying K+ conductance in cultured mouse peritoneal macrophages. , 1984, Proceedings of the National Academy of Sciences of the United States of America.

[52]  A. Nomeir,et al.  Blocking ion channel KCNN4 alleviates the symptoms of experimental autoimmune encephalomyelitis in mice , 2005, European journal of immunology.

[53]  K. Chandy,et al.  Selective blockade of T lymphocyte K+ channels ameliorates experimental autoimmune encephalomyelitis, a model for multiple sclerosis , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[54]  F. N. Quandt,et al.  Ion channel expression in PMA-differentiated human THP-1 macrophages. , 1996, The Journal of membrane biology.

[55]  Kuhlmann,et al.  Identification of glial cell proliferation in early multiple sclerosis lesions , 1998, Neuropathology and applied neurobiology.

[56]  B. Freedman,et al.  Modulation of Kv Channel Expression and Function by TCR and Costimulatory Signals during Peripheral CD4+ Lymphocyte Differentiation , 2002, The Journal of experimental medicine.

[57]  T. Waldmann,et al.  Humanized anti-CD25 (daclizumab) inhibits disease activity in multiple sclerosis patients failing to respond to interferon beta. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[58]  R. Biassoni,et al.  What is a natural killer cell? , 2002, Nature Immunology.

[59]  S. Miller,et al.  Epitope spreading in immune-mediated diseases: implications for immunotherapy , 2002, Nature Reviews Immunology.

[60]  Jacqueline Palace,et al.  The effect of anti-α4 integrin antibody on brain lesion activity in MS , 1999, Neurology.

[61]  J. Frank,et al.  Encephalitogenic potential of the myelin basic protein peptide (amino acids 83–99) in multiple sclerosis: Results of a phase II clinical trial with an altered peptide ligand , 2000, Nature Medicine.

[62]  F. A. Davis,et al.  4‐Aminopyridine in multiple sclerosis , 1991, Neurology.

[63]  P. Giraud,et al.  Selective Blocking of Voltage-Gated K+ Channels Improves Experimental Autoimmune Encephalomyelitis and Inhibits T Cell Activation1 , 2001, The Journal of Immunology.

[64]  R. North,et al.  Kv1.3 potassium channels in human alveolar macrophages. , 2003, American journal of physiology. Lung cellular and molecular physiology.

[65]  K. Chandy,et al.  Calmodulin Mediates Calcium-dependent Activation of the Intermediate Conductance KCa Channel,IKCa1 * , 1999, The Journal of Biological Chemistry.

[66]  B. Freedman,et al.  Identification of Kv1.1 Expression by Murine CD4−CD8− Thymocytes , 1995, The Journal of Biological Chemistry.

[67]  O. Pongs,et al.  Tyrosine Phosphorylation-dependent Suppression of a Voltage-gated K+ Channel in T Lymphocytes upon Fas Stimulation* , 1996, The Journal of Biological Chemistry.

[68]  K. Chandy,et al.  Mitogen induction of ion channels in murine T lymphocytes , 1987, The Journal of general physiology.

[69]  C. Deutsch,et al.  Diverse K+ channels in primary human T lymphocytes , 1992, The Journal of general physiology.

[70]  T. Yamamura,et al.  The regulatory role of natural killer cells in multiple sclerosis. , 2004, Brain : a journal of neurology.

[71]  R. Moots,et al.  Natural killer cells in the synovial fluid of rheumatoid arthritis patients exhibit a CD 56 bright , CD 94 bright , CD 158 negative phenotype , 2003 .

[72]  M. Álvarez-Mon,et al.  Active Crohn's Disease Patients Show a Distinctive Expansion of Circulating Memory CD4+CD45RO+CD28null T Cells , 2004, Journal of Clinical Immunology.

[73]  C. June,et al.  Decreased dependence of myelin basic protein-reactive T cells on CD28-mediated costimulation in multiple sclerosis patients. A marker of activated/memory T cells. , 1998 .

[74]  A. Bordey,et al.  Chemokine modulation of high‐conductance Ca2+‐sensitive K+ currents in microglia from human hippocampi , 2003, The European journal of neuroscience.

[75]  David H. Foster,et al.  Effects of 4-aminopyridine in patients with multiple sclerosis , 1983, Journal of the Neurological Sciences.

[76]  V. Gallo,et al.  Shaker‐type potassium channel subunits differentially control oligodendrocyte progenitor proliferation , 2004, Glia.

[77]  X. C. Wang,et al.  Abnormal naive and memory T lymphocyte subsets in the peripheral blood of patients with uveitis. , 1997, Current eye research.

[78]  C. Kernich.  Patient and family fact sheet. Current treatments for multiple sclerosis. , 2005, The neurologist.

[79]  G. Kaczorowski,et al.  Potent Kv1.3 inhibitors from correolide-modification of the C18 position. , 2005, Bioorganic & medicinal chemistry letters.

[80]  Z. Stelmasiak,et al.  Interleukin‐8 and RANTES levels in patients with relapsing–remitting multiple sclerosis (RR‐MS) treated with cladribine , 2004, Acta neurologica Scandinavica.

[81]  H. Hartung,et al.  The role of B cells and autoantibodies in multiple sclerosis , 2000, Annals of neurology.

[82]  H. Ochs,et al.  Functional analysis of human memory B-cell subpopulations: IgD+CD27+ B cells are crucial in secondary immune response by producing high affinity IgM. , 2003, Clinical immunology.

[83]  F. Sallusto,et al.  Two subsets of memory T lymphocytes with distinct homing potentials and effector functions , 1999, Nature.

[84]  P. Calabresi,et al.  The voltage-gated Kv1.3 K(+) channel in effector memory T cells as new target for MS. , 2003, The Journal of clinical investigation.

[85]  Richard S Lewis,et al.  Calcium signaling mechanisms in T lymphocytes. , 2001, Annual review of immunology.

[86]  S. Grissmer,et al.  Ca(2+)-activated K+ channels in human leukemic T cells , 1992, The Journal of general physiology.

[87]  O. McManus,et al.  Correolide and derivatives are novel immunosuppressants blocking the lymphocyte Kv1.3 potassium channels. , 1999, Cellular immunology.

[88]  M. Esiri,et al.  Immunohistological analysis of T lymphocyte subsets in the central nervous system in chronic progressive multiple sclerosis , 1983, Journal of the Neurological Sciences.

[89]  R. Moots,et al.  Natural killer cells in the synovial fluid of rheumatoid arthritis patients exhibit a CD56bright,CD94bright,CD158negative phenotype. , 2003, Rheumatology.

[90]  E. Christian,et al.  A Novel Gene, hKCa4, Encodes the Calcium-activated Potassium Channel in Human T Lymphocytes* , 1997, The Journal of Biological Chemistry.

[91]  David H. Miller,et al.  A controlled trial of natalizumab for relapsing multiple sclerosis. , 2003, The New England journal of medicine.

[92]  A. Uccelli,et al.  Recapitulation of B cell differentiation in the central nervous system of patients with multiple sclerosis. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[93]  K. Chandy,et al.  K+ Channel Expression during B Cell Differentiation: Implications for Immunomodulation and Autoimmunity1 , 2004, The Journal of Immunology.

[94]  E. Voth,et al.  Frequent detection of thyroid peroxidase‐specific IgG+ memory B cells in blood of patients with autoimmune thyroid disease , 2002, European journal of immunology.

[95]  J. V. Noort.  Developing antigen-specific therapies in multiple sclerosis: a tale of Tantalus or Ulysses? , 1999 .

[96]  H. Kolb,et al.  Transfer of insulin-dependent diabetes between HLA-identical siblings by bone marrow transplantation , 1993, The Lancet.

[97]  I. Cohen,et al.  The rapid isolation of clonable antigen‐specific T lymphocyte lines capable of mediating autoimmune encephalomyelitis , 1981, European journal of immunology.

[98]  K. Chandy,et al.  A voltage‐gated potassium channel in human T lymphocytes. , 1985, The Journal of physiology.

[99]  K. Rajewsky,et al.  Human Immunoglobulin (Ig)M+IgD+ Peripheral Blood B Cells Expressing the CD27 Cell Surface Antigen Carry Somatically Mutated Variable Region Genes: CD27 as a General Marker for Somatically Mutated (Memory) B Cells , 1998, The Journal of experimental medicine.

[100]  A. Engel,et al.  Immunocytochemical study of CD45 T cell isoforms in inflammatory myopathies. , 1995, The American journal of pathology.

[101]  N. Sigal,et al.  Blockade of the voltage-gated potassium channel Kv1.3 inhibits immune responses in vivo. , 1997, Journal of immunology.

[102]  H. Lester,et al.  Kir4.1 Potassium Channel Subunit Is Crucial for Oligodendrocyte Development and In Vivo Myelination , 2001, The Journal of Neuroscience.

[103]  S. Grissmer,et al.  K+ channel types targeted by synthetic OSK1, a toxin from Orthochirus scrobiculosus scorpion venom. , 2005, The Biochemical journal.

[104]  J. Masjuán,et al.  Intrathecal synthesis of oligoclonal IgM against myelin lipids predicts an aggressive disease course in MS. , 2005, The Journal of clinical investigation.

[105]  David E. Anderson,et al.  Multiple sclerosis. , 2005, Immunological Reviews.

[106]  A. Koschak,et al.  Subunit Composition of Brain Voltage-gated Potassium Channels Determined by Hongotoxin-1, a Novel Peptide Derived fromCentruroides limbatus Venom* , 1998, The Journal of Biological Chemistry.

[107]  K. Whaley,et al.  Decreased Total Numbers of Peripheral Blood Lymphocytes with Elevated Percentages of CD4+CD45RO+ and CD4+CD25+ of T‐Helper Cells in Non‐Segmental Vitiligo , 2002, The Journal of dermatology.

[108]  M. Wasko,et al.  Fc gamma R expression on NK cells influences disease severity in rheumatoid arthritis. , 2004, Genes and immunity.

[109]  F. Kirchhoff,et al.  Heterogeneous expression of voltage-gated potassium channels of the shaker family (Kv1) in oligodendrocyte progenitors , 1999, Brain Research.

[110]  I. Mackay,et al.  T cell necessity in the pathogenesis of experimental autoimmune encephalomyelitis in mice , 1976, European journal of immunology.

[111]  P. Stastny,et al.  Desmoglein-1-specific T lymphocytes from patients with endemic pemphigus foliaceus (fogo selvagem). , 2000, The Journal of clinical investigation.

[112]  S. Hagiwara,et al.  Potassium channels in human NK cells are involved in discrete stages of the killing process. , 1986, Journal of immunology.

[113]  K. Chandy,et al.  Altered K+ channel expression in abnormal T lymphocytes from mice with the lpr gene mutation. , 1986, Science.

[114]  S. Todesco,et al.  Early phenotypic activation of circulating helper memory T cells in scleroderma: correlation with disease activity. , 1993, Annals of the rheumatic diseases.

[115]  K. Chandy,et al.  Voltage-gated potassium channels are required for human T lymphocyte activation , 1984, The Journal of experimental medicine.

[116]  F. N. Quandt,et al.  III. Ion Channel Expression in PMA-differentiated Human THP-1 Macrophages , 1996, The Journal of Membrane Biology.

[117]  Mark J. Miller,et al.  Up-regulation of the IKCa1 Potassium Channel during T-cell Activation , 2000, The Journal of Biological Chemistry.

[118]  D. Hafler,et al.  Amendment history : Corrigendum ( June 2002 ) GAD 65-reactive T cells are activated in patients with autoimmune type 1 a diabetes , 2018 .

[119]  P. Pennefather,et al.  HERG-like K+ Channels in Microglia , 1998, The Journal of general physiology.