Kv1.3 deletion biases T cells toward an immunoregulatory phenotype and renders mice resistant to autoimmune encephalomyelitis

Anne R. Gocke, Lori A. Lebson, Inna V. Grishkan, Lina Hu, Hai M. Nguyen, Katharine A. Whartenby, K. George Chandy, Peter A. Calabresi

Research output: Contribution to journalArticlepeer-review

53 Scopus citations


Increasing evidence suggests ion channels have critical functions in the differentiation and plasticity of T cells. Kv1.3, a voltage-gated K + channel, is a functional marker and a pharmacological target for activated effector memory T cells. Selective Kv1.3 blockers have been shown to inhibit proliferation and cytokine production by human and rat effector memory T cells. We used Kv1.3 knockout (KO) mice to investigate the mechanism by which Kv1.3 blockade affects CD4 + T cell differentiation during an inflammatory immune-mediated disease. Kv1.3 KO animals displayed significantly lower incidence and severity of myelin oligodendrocyte glycoprotein (MOG) peptide-induced experimental autoimmune encephalomyelitis. Kv1.3 was the only KV channel expressed in MOG 35-55-specific CD4 + T cell blasts, and no KV current was present in MOG-specific CD4 + T cell-blasts from Kv1.3 KO mice. Fewer CD4 + T cells migrated to the CNS in Kv1.3 KO mice following disease induction, and Ag-specific proliferation of CD4 + T cells from these mice was impaired with a corresponding cell-cycle delay. Kv1.3 was required for optimal expression of IFN-γ and IL-17, whereas its absence led to increased IL-10 production. Dendritic cells from Kv1.3 KO mice fully activated wild-type CD4 + T cells, indicating a T cell-intrinsic defect in Kv1.3 KO mice. The loss of Kv1.3 led to a suppressive phenotype, which may contribute to the mechanism by which deletion of Kv1.3 produces an immunotherapeutic effect. Skewing of CD4 + T cell differentiation toward Ag-specific regulatory T cells by pharmacological blockade or genetic suppression of Kv1.3 might be beneficial for therapy of immune-mediated diseases such as multiple sclerosis.

Original languageEnglish (US)
Pages (from-to)5877-5886
Number of pages10
JournalJournal of Immunology
Issue number12
StatePublished - Jun 15 2012

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology


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