title: CD8+ T Cells Regulate Monopoiesis and Circulating Ly6C-high Monocyte Levels in Atherosclerosis in Mice.
abstract: BACKGROUND
  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.
  
  
  RESULTS
  We observed that CD8(+) 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 (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-γ neutralization, showing a role for interferon-γ.
  
  
  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.
authors.affiliation: From the Institute of Clinical Biochemistry and Pathobiochemistry, University Hospital Würzburg (C.C., M.K., S.M.C., A.Z.) and Rudolf Virchow Center (M.B.), University of Würzburg, Würzburg, Germany; Department of Vascular Surgery, Klinikum rechts der Isar, Technical University Munich, Munich, Germany (J.P.); and Bioceros, Utrecht, The Netherlands (L.B.).
authors.forename: Clément
authors.initials: C
authors.lastname: Cochain
authors.affiliation: From the Institute of Clinical Biochemistry and Pathobiochemistry, University Hospital Würzburg (C.C., M.K., S.M.C., A.Z.) and Rudolf Virchow Center (M.B.), University of Würzburg, Würzburg, Germany; Department of Vascular Surgery, Klinikum rechts der Isar, Technical University Munich, Munich, Germany (J.P.); and Bioceros, Utrecht, The Netherlands (L.B.).
authors.forename: Miriam
authors.initials: M
authors.lastname: Koch
authors.affiliation: From the Institute of Clinical Biochemistry and Pathobiochemistry, University Hospital Würzburg (C.C., M.K., S.M.C., A.Z.) and Rudolf Virchow Center (M.B.), University of Würzburg, Würzburg, Germany; Department of Vascular Surgery, Klinikum rechts der Isar, Technical University Munich, Munich, Germany (J.P.); and Bioceros, Utrecht, The Netherlands (L.B.).
authors.forename: Sweena M
authors.initials: SM
authors.lastname: Chaudhari
authors.affiliation: From the Institute of Clinical Biochemistry and Pathobiochemistry, University Hospital Würzburg (C.C., M.K., S.M.C., A.Z.) and Rudolf Virchow Center (M.B.), University of Würzburg, Würzburg, Germany; Department of Vascular Surgery, Klinikum rechts der Isar, Technical University Munich, Munich, Germany (J.P.); and Bioceros, Utrecht, The Netherlands (L.B.).
authors.forename: Martin
authors.initials: M
authors.lastname: Busch
authors.affiliation: From the Institute of Clinical Biochemistry and Pathobiochemistry, University Hospital Würzburg (C.C., M.K., S.M.C., A.Z.) and Rudolf Virchow Center (M.B.), University of Würzburg, Würzburg, Germany; Department of Vascular Surgery, Klinikum rechts der Isar, Technical University Munich, Munich, Germany (J.P.); and Bioceros, Utrecht, The Netherlands (L.B.).
authors.forename: Jaroslav
authors.initials: J
authors.lastname: Pelisek
authors.affiliation: From the Institute of Clinical Biochemistry and Pathobiochemistry, University Hospital Würzburg (C.C., M.K., S.M.C., A.Z.) and Rudolf Virchow Center (M.B.), University of Würzburg, Würzburg, Germany; Department of Vascular Surgery, Klinikum rechts der Isar, Technical University Munich, Munich, Germany (J.P.); and Bioceros, Utrecht, The Netherlands (L.B.).
authors.forename: Louis
authors.initials: L
authors.lastname: Boon
authors.affiliation: From the Institute of Clinical Biochemistry and Pathobiochemistry, University Hospital Würzburg (C.C., M.K., S.M.C., A.Z.) and Rudolf Virchow Center (M.B.), University of Würzburg, Würzburg, Germany; Department of Vascular Surgery, Klinikum rechts der Isar, Technical University Munich, Munich, Germany (J.P.); and Bioceros, Utrecht, The Netherlands (L.B.). alma.zernecke@uni-wuerzburg.de.
authors.forename: Alma
authors.initials: A
authors.lastname: Zernecke
mesh_terms: D000818:Animals; D000950:Antigens, Ly / Q000032:analysis*; D000961:Antilymphocyte Serum / Q000627:therapeutic use; D050197:Atherosclerosis / Q000209:etiology / Q000276:immunology*; D001853:Bone Marrow / Q000378:metabolism / Q000473:pathology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D016893:Carotid Stenosis / Q000276:immunology / Q000473:pathology; D002478:Cells, Cultured; D002634:Chemotaxis, Leukocyte / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D004036:Diet, Atherogenic / Q000009:adverse effects; D004041:Dietary Fats / Q000633:toxicity; D016894:Endarterectomy, Carotid; D005786:Gene Expression Regulation / Q000276:immunology; D006801:Humans; D006937:Hypercholesterolemia / Q000150:complications / Q000209:etiology; D007371:Interferon-gamma / Q000502:physiology; D008264:Macrophages / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009000:Monocytes / Q000276:immunology*; D038042:Myelopoiesis / Q000276:immunology*; D011973:Receptors, LDL / Q000172:deficiency / Q000235:genetics
chemical_list: D000950:Antigens, Ly; D000961:Antilymphocyte Serum; D016207:Cytokines; D004041:Dietary Fats; C494192:Ly-6C antigen, mouse; D011973:Receptors, LDL; D007371:Interferon-gamma
keywords: atherosclerosis; inflammation; lymphocytes; monocytes