Interleukin 12 induces T-cell recruitment into the atherosclerotic plaque

Xiaoyu Zhang, Alexander Niessner, Takako Nakajima, Wei Ma-Krupa, Stephen L. Kopecky, Robert L. Frye, Jörg J. Goronzy, Cornelia M. Weyand

Research output: Contribution to journalArticlepeer-review

93 Scopus citations

Abstract

CD4 T cells, through the release of cytokines as well as direct effector functions, have been implicated in promoting inflammation of the atherosclerotic plaque. Plaque-infiltrating CD4 T cells include a specialized subset of CD4+CD28- T cells that express a unique profile of regulatory receptors and are responsive to novel microenvironmental cues. Here we report that CD4+CD28- T cells, either isolated from the plaque tissue or from the blood of patients with acute coronary syndrome (ACS), spontaneously express interleukin (IL)-12 receptors, even in the absence of antigenic stimulation. CD4+CD28- IL-12R+ cells responded to IL-12 stimulation with the upregulation of the chemokine receptor CCR5 and the C-type lectin receptor CD161, both implicated in regulating tissue homing of effector T cells. IL-12 treatment of CD4+CD28- T cells enhanced their chemotaxis and transendothelial migration toward the chemokine CCL5. In vivo relevance for the role of IL-12 in regulating the recruitment of CD4+CD28- T cells into the atheroma was examined in human atheroma-SCID mouse chimeras. Exposure of nonstimulated CD4+CD28- T cells to IL-12 was sufficient to amplify T-cell accumulation within the inflamed plaque, and coadministration of anti-CCR5 antibodies blocked T-cell recruitment into the plaque. Thus, CD4 +CD28- T cells functionally resemble NK cells, which have proinflammatory activity even in the unprimed state and respond to any IL-12-inducing host infection with a shift in tissue trafficking and accrual in inflammatory lesions.

Original languageEnglish (US)
Pages (from-to)524-531
Number of pages8
JournalCirculation research
Volume98
Issue number4
DOIs
StatePublished - Mar 2006

Keywords

  • Cytokines
  • Inflammation
  • Interleukins
  • T lymphocyte
  • Vascular inflammation

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

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