title: Cholesterol lowering modulates T cell function in vivo and in vitro.
abstract: BACKGROUND
  The lipid milleu exacerbates the inflammatory response in atherosclerosis but its effect on T cell mediated immune response has not been fully elucidated. We hypothesized that lipid lowering would modulate T cell mediated immune function.
  
  
  RESULTS
  T cells isolated from human PBMC or splenic T cells from apoE-/- mouse had higher proliferative response to T cell receptor (TCR) ligation in medium supplemented with 10% fetal bovine serum (FBS) compared to medium with 10% delipidated FBS. The differences in proliferation were associated with changes in lipid rafts, cellular cholesterol content, IL-10 secretion and subsequent activation of signaling molecule activated by TCR ligation. Immune biomarkers were also assessed in vivo using male apoE-/- mice fed atherogenic diet (AD) starting at 7 weeks of age. At 25 weeks of age, a sub-group was switched to normal diet (ND) whereas the rest remained on AD until euthanasia at 29 weeks of age. Dietary change resulted in a lower circulating level of cholesterol, reduced plaque size and inflammatory phenotype of plaques. These changes were associated with reduced intracellular IL-10 and IL-12 expression in CD4+ and CD8+ T cells.
  
  
  CONCLUSIONS
  Our results show that lipid lowering reduces T cell proliferation and function, supporting the notion that lipid lowering modulates T cell function in vivo and in vitro.
authors.affiliation: Oppenheimer Atherosclerosis Research Center, Division of Cardiology, Cedars-Sinai Heart Institute, Cedars-Sinai Medical Center, Los Angeles, California, United States of America.
authors.forename: Kuang-Yuh
authors.initials: KY
authors.lastname: Chyu
authors.affiliation: Oppenheimer Atherosclerosis Research Center, Division of Cardiology, Cedars-Sinai Heart Institute, Cedars-Sinai Medical Center, Los Angeles, California, United States of America.
authors.forename: Wai Man
authors.initials: WM
authors.lastname: Lio
authors.affiliation: Oppenheimer Atherosclerosis Research Center, Division of Cardiology, Cedars-Sinai Heart Institute, Cedars-Sinai Medical Center, Los Angeles, California, United States of America.
authors.forename: Paul C
authors.initials: PC
authors.lastname: Dimayuga
authors.affiliation: Oppenheimer Atherosclerosis Research Center, Division of Cardiology, Cedars-Sinai Heart Institute, Cedars-Sinai Medical Center, Los Angeles, California, United States of America.
authors.forename: Jianchang
authors.initials: J
authors.lastname: Zhou
authors.affiliation: Oppenheimer Atherosclerosis Research Center, Division of Cardiology, Cedars-Sinai Heart Institute, Cedars-Sinai Medical Center, Los Angeles, California, United States of America.
authors.forename: Xiaoning
authors.initials: X
authors.lastname: Zhao
authors.affiliation: Oppenheimer Atherosclerosis Research Center, Division of Cardiology, Cedars-Sinai Heart Institute, Cedars-Sinai Medical Center, Los Angeles, California, United States of America.
authors.forename: Juliana
authors.initials: J
authors.lastname: Yano
authors.affiliation: Oppenheimer Atherosclerosis Research Center, Division of Cardiology, Cedars-Sinai Heart Institute, Cedars-Sinai Medical Center, Los Angeles, California, United States of America.
authors.forename: Portia
authors.initials: P
authors.lastname: Trinidad
authors.affiliation: Oppenheimer Atherosclerosis Research Center, Division of Cardiology, Cedars-Sinai Heart Institute, Cedars-Sinai Medical Center, Los Angeles, California, United States of America.
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Honjo
authors.affiliation: Oppenheimer Atherosclerosis Research Center, Division of Cardiology, Cedars-Sinai Heart Institute, Cedars-Sinai Medical Center, Los Angeles, California, United States of America.
authors.forename: Bojan
authors.initials: B
authors.lastname: Cercek
authors.affiliation: Oppenheimer Atherosclerosis Research Center, Division of Cardiology, Cedars-Sinai Heart Institute, Cedars-Sinai Medical Center, Los Angeles, California, United States of America.
authors.forename: Prediman K
authors.initials: PK
authors.lastname: Shah
mesh_terms: D000818:Animals; D001057:Apolipoproteins E / Q000172:deficiency / Q000378:metabolism; D015153:Blotting, Western; D049109:Cell Proliferation / Q000187:drug effects; D002469:Cell Separation; D002784:Cholesterol / Q000097:blood / Q000378:metabolism*; D003470:Culture Media / Q000494:pharmacology; D004041:Dietary Fats / Q000494:pharmacology; D004797:Enzyme-Linked Immunosorbent Assay; D004951:Esterification; D006801:Humans; D016753:Interleukin-10 / Q000378:metabolism; D008213:Lymphocyte Activation / Q000187:drug effects; D008297:Male; D021962:Membrane Microdomains / Q000187:drug effects / Q000378:metabolism; D008810:Mice, Inbred C57BL; D010766:Phosphorylation / Q000187:drug effects; D058226:Plaque, Atherosclerotic / Q000473:pathology; D012850:Sinus of Valsalva / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D051746:ZAP-70 Protein-Tyrosine Kinase / Q000378:metabolism
chemical_list: D001057:Apolipoproteins E; D003470:Culture Media; D004041:Dietary Fats; D016753:Interleukin-10; D002784:Cholesterol; D051746:ZAP-70 Protein-Tyrosine Kinase; C497262:Zap70 protein, mouse