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

被引：171

作者：

Matheu, Melanie P. ^{[1
,2
]}

Beeton, Christine ^{[1
,2
]}

Garcia, Adriana ^{[1
,2
]}

Chi, Victor ^{[1
,2
]}

Rangaraju, Srikant ^{[1
,2
]}

Safrina, Olga ^{[1
,2
]}

Monaghan, Kevin ^{[1
,2
]}

Uemura, Marc I. ^{[1
,2
]}

Li, Dan ^{[3
]}

Pal, Sukumar ^{[3
]}

de la Maza, Luis M. ^{[3
]}

Monuki, Edwin ^{[3
]}

Fluegel, Alexander ^{[5
]}

Pennington, Michael W. ^{[6
]}

Parker, Ian ^{[1
,2
,4
]}

Chandy, K. George ^{[1
,2
]}

Cahalan, Michael D. ^{[1
,2
]}

机构：

[1] Univ Calif Irvine, Dept Physiol & Biophys, Irvine, CA 92697 USA

[2] Univ Calif Irvine, Ctr Immunol, Irvine, CA 92697 USA

[3] Univ Calif Irvine, Dept Pathol, Irvine, CA 92697 USA

[4] Univ Calif Irvine, Dept Neurobiol & Behav, Irvine, CA 92697 USA

[5] Max Planck Inst Neurobiol, Dept Neuroimmunol, D-82152 Martinsried, Germany

[6] Bachem Biosci Inc, King Of Prussia, PA 19406 USA

来源：

IMMUNITY | 2008年 / 29卷 / 04期

关键词：

D O I：

10.1016/j.immuni.2008.07.015

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

Effector memory T (Tem) cells are essential mediators of autoimmune disease and delayed-type hypersensitivity (DTH), a convenient model for two-photon imaging of Tern 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 Tern cells were highly motile along collagen fibers and continued to migrate rapidly for 18 hr. Tern cells rely on voltagegated 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.

引用

页码：602 / 614

页数：13

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