Antigenic stimulation of Kv1.3-deficient Th cells gives rise to a population of Foxp3-independent T cells with suppressive properties

Inna V. Grishkan, Dominique M. Tosi, Melissa D. Bowman, Maya Harary, Peter Calabresi, Anne R. Gocke

Research output: Contribution to journalArticle

Abstract

Multiple sclerosis (MS) is an immune-mediated demyelinating disease of the CNS that has been linked with defects in regulatory T cell function. Therefore, strategies to selectively target pathogenic cells via enhanced regulatory T cell activity may provide therapeutic benefit. Kv1.3 is a voltage-gated potassium channel expressed on myelin-reactive T cells from MS patients. Kv1.3- knockout (KO) mice are protected from experimental autoimmune encephalomyelitis, an animal model of MS, and Kv1.3-KO Th cells display suppressive capacity associated with increased IL-10. In this article, we demonstrate that myelin oligodendrocyte glycoprotein-specific Kv1.3-KO Th cells exhibit a unique regulatory phenotype characterized by high CD25, CTLA4, pSTAT5, FoxO1, and GATA1 expression without a corresponding increase in Foxp3. These phenotypic changes result from increased signaling through IL-2R. Moreover, myelin oligodendrocyte glycoprotein-specific Kv1.3-KO Th cells can ameliorate experimental autoimmune encephalomyelitis following transfer to wild-type recipients in a manner that is partially dependent on IL-2R and STAT5 signaling. The present study identifies a population of Foxp32 T cells with suppressive properties that arises in the absence of Kv1.3 and enhances the understanding of the molecular mechanism by which these cells are generated. This increased understanding could contribute to the development of novel therapies for MS patients that promote heightened immune regulation.

Original languageEnglish (US)
Pages (from-to)1399-1407
Number of pages9
JournalJournal of Immunology
Volume195
Issue number4
DOIs
StatePublished - Aug 15 2015

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Multiple Sclerosis
T-Lymphocytes
Myelin-Oligodendrocyte Glycoprotein
Autoimmune Experimental Encephalomyelitis
Population
Regulatory T-Lymphocytes
Voltage-Gated Potassium Channels
Demyelinating Diseases
Myelin Sheath
Knockout Mice
Interleukin-10
Animal Models
Phenotype
Therapeutics

ASJC Scopus subject areas

  • Immunology

Cite this

Antigenic stimulation of Kv1.3-deficient Th cells gives rise to a population of Foxp3-independent T cells with suppressive properties. / Grishkan, Inna V.; Tosi, Dominique M.; Bowman, Melissa D.; Harary, Maya; Calabresi, Peter; Gocke, Anne R.

In: Journal of Immunology, Vol. 195, No. 4, 15.08.2015, p. 1399-1407.

Research output: Contribution to journalArticle

Grishkan, Inna V. ; Tosi, Dominique M. ; Bowman, Melissa D. ; Harary, Maya ; Calabresi, Peter ; Gocke, Anne R. / Antigenic stimulation of Kv1.3-deficient Th cells gives rise to a population of Foxp3-independent T cells with suppressive properties. In: Journal of Immunology. 2015 ; Vol. 195, No. 4. pp. 1399-1407.
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