Imaging of Effector Memory T Cells During a Delayed-type Hypersensitivity Reaction and Suppression by Kv1.3 Channel Block

Overview

Journal Immunity

Publisher Cell Press

Specialty Allergy & Immunology

Date 2008 Oct 7

PMID 18835197

Citations 126

Authors

Melanie P Matheu

Christine Beeton

Adriana Garcia

Victor Chi

Srikant Rangaraju

Olga Safrina

Kevin Monaghan

Marc I Uemura

Dan Li

Sukumar Pal

Luis M de la Maza

Edwin Monuki

Alexander Flugel

Michael W Pennington

Ian Parker

K George Chandy

Michael D Cahalan

Affiliations

Soon will be listed here.

Abstract

Effector memory T (Tem) cells are essential mediators of autoimmune disease and delayed-type hypersensitivity (DTH), a convenient model for two-photon imaging of Tem cell participation in an inflammatory response. Shortly (3 hr) after entry into antigen-primed ear tissue, Tem cells stably attached to antigen-bearing antigen-presenting cells (APCs). After 24 hr, enlarged Tem cells were highly motile along collagen fibers and continued to migrate rapidly for 18 hr. Tem cells rely on voltage-gated Kv1.3 potassium channels to regulate calcium signaling. ShK-186, a specific Kv1.3 blocker, inhibited DTH and suppressed Tem cell enlargement and motility in inflamed tissue but had no effect on homing to or motility in lymph nodes of naive and central memory T (Tcm) cells. ShK-186 effectively treated disease in a rat model of multiple sclerosis. These results demonstrate a requirement for Kv1.3 channels in Tem cells during an inflammatory immune response in peripheral tissues. Targeting Kv1.3 allows for effector memory responses to be suppressed while central memory responses remain intact.

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