| First Author | Cochain C | Year | 2015 |
| Journal | Circ Res | Volume | 117 |
| Issue | 3 | Pages | 244-53 |
| PubMed ID | 25991812 | Mgi Jnum | J:256888 |
| Mgi Id | MGI:6098814 | Doi | 10.1161/CIRCRESAHA.117.304611 |
| Citation | Cochain C, et al. (2015) CD8+ T Cells Regulate Monopoiesis and Circulating Ly6C-high Monocyte Levels in Atherosclerosis in Mice. Circ Res 117(3):244-53 |
| abstractText | RATIONALE: Proinflammatory adaptive immune responses are recognized as major drivers of atherosclerotic lesion formation. Although CD8(+) T cells have recently been proposed as a proatherogenic cell subset, their full scope of actions remains to be elucidated. OBJECTIVE: We here addressed the contribution of CD8(+) T cells to monocyte trafficking in atherosclerosis. METHOD AND RESULTS: We observed that CD8(+) T cells express proinflammatory cytokines (interferon-gamma, tumor necrosis factor-alpha, and interleukin-12) within atherosclerotic lesions and spleens of high-fat diet-fed low-density lipoprotein receptor-deficient (Ldlr(-/-)) mice. Antibody-mediated CD8(+) T-cell depletion in high-fat diet-fed Ldlr(-/-) 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(+) T-cell depletion did not directly affect monocyte recruitment to inflamed vessels. However, CD8(+) T-cell depletion decreased chemokine (CC-motif) ligand serum concentrations and circulating Ly6C(high) monocyte counts. We further evidenced that CD8(+) 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-gamma neutralization, showing a role for interferon-gamma. CONCLUSIONS: These data suggest that CD8(+) 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. |
