Interleukin 12 induces T-cell recruitment into the atherosclerotic plaque.
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.
Zhang
Xiaoyu
X
Department of Medicine, Kathleen B. and Mason I. Lowance Center for Human Immunology, Emory University School of Medicine, Atlanta, GA, USA.
Niessner
Alexander
A
Nakajima
Takako
T
Ma-Krupa
Wei
W
Kopecky
Stephen L
SL
Frye
Robert L
RL
Goronzy
Jörg J
JJ
Weyand
Cornelia M
CM
D000368:Aged; D000818:Animals; D050197:Atherosclerosis / Q000276:immunology / Q000473:pathology*; D018106:CD28 Antigens / Q000032:analysis; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects* / Q000502:physiology; D002465:Cell Movement / Q000187:drug effects; D002633:Chemotaxis / Q000187:drug effects; D003327:Coronary Disease / Q000276:immunology; D005260:Female; D006801:Humans; D018664:Interleukin-12 / Q000494:pharmacology*; D008297:Male; D051379:Mice; D016513:Mice, SCID; D019713:Receptors, CCR5 / Q000502:physiology; D018123:Receptors, Interleukin / Q000032:analysis; D053707:Receptors, Interleukin-12
D018106:CD28 Antigens; D019713:Receptors, CCR5; D018123:Receptors, Interleukin; D053707:Receptors, Interleukin-12; D018664:Interleukin-12