CD8+ T Cells Regulate Monopoiesis and Circulating Ly6Chigh Monocyte Levels in Atherosclerosis in Mice. Issue 3 (17th July 2015)

• Record Type: Journal Article
• Authors: Cochain, Clément; Koch, Miriam; Chaudhari, Sweena M.; Busch, Martin; Pelisek, Jaroslav; Boon, Louis; Zernecke, Alma
• Is Part Of: Circulation research. Volume 117:Issue 3(2015)
• Publication Date: 2015-07-17
• Subjects: Cardiovascular system -- Periodicals; Blood -- Circulation -- Periodicals; Blood Circulation; Cardiovascular System; Vascular Diseases; Sang -- Circulation -- Périodiques; Appareil cardiovasculaire -- Périodiques; 612.1
• DOI: 10.1161/CIRCRESAHA.117.304611
• Languages: English
• ISSNs: 0009-7330

Abstract

<abstract> <title> <x xml:space="preserve">Abstract</x> </title> <sec> <title> <underline>Rationale:</underline> </title> <p>Proinflammatory adaptive immune responses are recognized as major drivers of atherosclerotic lesion formation. Although CD8<sup>+</sup> T cells have recently been proposed as a proatherogenic cell subset, their full scope of actions remains to be elucidated.</p> </sec> <sec> <title> <underline>Objective:</underline> </title> <p>We here addressed the contribution of CD8<sup>+</sup> T cells to monocyte trafficking in atherosclerosis.</p> </sec> <sec> <title> <underline>Method and Results:</underline> </title> <p>We observed that CD8<sup>+</sup> T cells express proinflammatory cytokines (interferon-γ, tumor necrosis factor-α, and interleukin-12) within atherosclerotic lesions and spleens of high-fat diet–fed low-density lipoprotein receptor–deficient (<italic>Ldlr</italic><sup>−/−</sup>) mice. Antibody-mediated CD8<sup>+</sup> T-cell depletion in high-fat diet–fed <italic>Ldlr</italic><sup>−/−</sup> mice decreased atherosclerotic plaque formation, associated with decreased macrophage accumulation within lesions. Despite a reduction in vascular chemokine (CC-motif) ligand 2 and chemokine (CXC-motif) ligand 1 expression, CD8<sup>+</sup> T-cell depletion did not directly affect monocyte recruitment to inflamed vessels. However, CD8<sup>+</sup> T-cell depletion decreased chemokine (CC-motif) ligand serum concentrations and circulating Ly6C<sup>high</sup> monocyte counts. We further evidenced that CD8<sup>+</sup> T-cell depletion decreased levels of mature monocytes and myeloid granulocyte–monocyte progenitors in the bone marrow and spleen of hypercholesterolemic mice, effects that were partially reproduced by interferon-γ neutralization, showing a role for interferon-γ.</p> </sec> <sec> <title> <underline>Conclusions:</underline> </title> <p>These data suggest that CD8<sup>+</sup> T cells promote atherosclerosis by controlling monopoiesis and circulating monocyte levels, which ultimately contributes to plaque macrophage burden without affecting direct monocyte recruitment, identifying this cell subset as a critical regulator of proatherogenic innate immune cell responses in atherosclerosis.</p> </sec> </abstract>