The voltage-gated Kv1.3 K+ channel in effector memory T cells as new target for MS

Heike Wulff, Peter A. Calabresi, Rameeza Allie, Sung Yun, Michael Pennington, Christine Beeton, K. George Chandy

Research output: Contribution to journalArticle

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Abstract

Through a combination of fluorescence microscopy and patch-clamp analysis we have identified a striking alteration in K+ channel expression in terminally differentiated human CCR7-CD45RA-effector memory T lymphocytes (TEM). Following activation, TEM cells expressed significantly higher levels of the voltage-gated K+ channel Kv1.3 and lower levels of the calcium-activated K+ channel IKCA1 than naive and central memory T cells (TCM). Upon repeated in vitro antigenic stimulation, naive cells differentiated into Kv1.3 highIKCa1low TEM cells, and the potent Kv1.3-blocking sea anemone Stichodactyla helianthus peptide (ShK) suppressed proliferation of TEM cells without affecting naive or TCM lymphocytes. Thus, the Kv1.3highIKCa1low phenotype is a functional marker of activated TEM lymphocytes. Activated myelin-reactive T cells from patients with MS exhibited the Kv1.3 highIKCa1low TEM phenotype, suggesting that they have undergone repeated stimulation during the course of disease; these cells may contribute to disease pathogenesis due to their ability to home to inflamed tissues and exhibit immediate effector function. The Kv1.3 highIKCa1low phenotype was not seen in glutamic acid decarboxylase, insulin-peptide or ovalbumin-specific and mitogen-activated T cells from MS patients, or in myelin-specific T cells from healthy controls. Selective targeting of Kv1.3 in TEM cells may therefore hold therapeutic promise for MS and other T cell-mediated autoimmune diseases.

Original languageEnglish (US)
Pages (from-to)1703-1713
Number of pages11
JournalJournal of Clinical Investigation
Volume111
Issue number11
StatePublished - Jun 2003

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Voltage-Gated Potassium Channels
T-Lymphocytes
Myelin Sheath
Phenotype
Sea Anemones
Lymphocytes
Calcium-Activated Potassium Channels
Peptides
Glutamate Decarboxylase
Helianthus
Ovalbumin
Mitogens
Fluorescence Microscopy
Autoimmune Diseases
Cell Proliferation
Insulin

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Wulff, H., Calabresi, P. A., Allie, R., Yun, S., Pennington, M., Beeton, C., & Chandy, K. G. (2003). The voltage-gated Kv1.3 K+ channel in effector memory T cells as new target for MS. Journal of Clinical Investigation, 111(11), 1703-1713.

The voltage-gated Kv1.3 K+ channel in effector memory T cells as new target for MS. / Wulff, Heike; Calabresi, Peter A.; Allie, Rameeza; Yun, Sung; Pennington, Michael; Beeton, Christine; Chandy, K. George.

In: Journal of Clinical Investigation, Vol. 111, No. 11, 06.2003, p. 1703-1713.

Research output: Contribution to journalArticle

Wulff, H, Calabresi, PA, Allie, R, Yun, S, Pennington, M, Beeton, C & Chandy, KG 2003, 'The voltage-gated Kv1.3 K+ channel in effector memory T cells as new target for MS', Journal of Clinical Investigation, vol. 111, no. 11, pp. 1703-1713.
Wulff H, Calabresi PA, Allie R, Yun S, Pennington M, Beeton C et al. The voltage-gated Kv1.3 K+ channel in effector memory T cells as new target for MS. Journal of Clinical Investigation. 2003 Jun;111(11):1703-1713.
Wulff, Heike ; Calabresi, Peter A. ; Allie, Rameeza ; Yun, Sung ; Pennington, Michael ; Beeton, Christine ; Chandy, K. George. / The voltage-gated Kv1.3 K+ channel in effector memory T cells as new target for MS. In: Journal of Clinical Investigation. 2003 ; Vol. 111, No. 11. pp. 1703-1713.
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