title: Role of naturally occurring CD4+ CD25+ regulatory T cells in experimental atherosclerosis.
abstract: OBJECTIVE
  Naturally occurring CD4+ CD25+ regulatory T cells (Tregs) exert suppressive effects on effector CD4 cells and downregulate experimental autoimmune disorders. We investigated the importance and potential role of Tregs in murine atherogenesis.
  
  
  RESULTS
  Tregs were investigated comparatively between aged and young apolipoprotein E-knockout (ApoE-KO) mice and age-matched C57BL/6 littermates. The effect of oxidized LDL (oxLDL) was tested on the functional suppressive properties of Tregs from ApoE-KO and C57BL/6 mice. Tregs, CD4+ CD25- cells, and saline were infused into ApoE-KO mice to study their effects on atherogenesis. Treg numbers were reduced in atherosclerotic compared with nonatherosclerotic ApoE-KO mice. The functional suppressive properties of Tregs from ApoE-KO mice were compromised in comparison with those from their C57BL/6 littermates. Thus, oxLDL attenuated the suppressive properties of Tregs from C57BL/6 mice and more so in ApoE-KO mice. Transfer of Tregs from age-matched ApoE-KO mice resulted in significant attenuation of atherosclerosis compared with that after delivery of CD4+ CD25+/- T cells or phosphate-buffered saline.
  
  
  CONCLUSIONS
  CD4+ CD25+ Tregs may play a protective role in the progression of atherosclerosis and could be considered a therapeutic tool if results from human studies can solidify observations in murine models.
authors.affiliation: Department of Cardiology, Tel Aviv Sourasky Medical Center, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Adi
authors.initials: A
authors.lastname: Mor
authors.forename: David
authors.initials: D
authors.lastname: Planer
authors.forename: Galia
authors.initials: G
authors.lastname: Luboshits
authors.forename: Arnon
authors.initials: A
authors.lastname: Afek
authors.forename: Shula
authors.initials: S
authors.lastname: Metzger
authors.forename: Tova
authors.initials: T
authors.lastname: Chajek-Shaul
authors.forename: Gad
authors.initials: G
authors.lastname: Keren
authors.forename: Jacob
authors.initials: J
authors.lastname: George
mesh_terms: D000375:Aging; D000818:Animals; D001011:Aorta / Q000378:metabolism / Q000473:pathology; D001057:Apolipoproteins E / Q000172:deficiency*; D050197:Atherosclerosis / Q000209:etiology* / Q000473:pathology* / Q000517:prevention & control; D015153:Blotting, Western; D002478:Cells, Cultured; D018920:Coculture Techniques; D018450:Disease Progression; D015536:Down-Regulation; D051858:Forkhead Transcription Factors / Q000378:metabolism; D016753:Interleukin-10 / Q000235:genetics; D053645:Interleukin-2 Receptor alpha Subunit / Q000172:deficiency / Q000378:metabolism*; D008077:Lipoproteins, LDL / Q000494:pharmacology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D012333:RNA, Messenger / Q000378:metabolism; D012850:Sinus of Valsalva / Q000378:metabolism / Q000473:pathology; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology / Q000637:transplantation
chemical_list: D001057:Apolipoproteins E; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D053645:Interleukin-2 Receptor alpha Subunit; D008077:Lipoproteins, LDL; D012333:RNA, Messenger; C099252:oxidized low density lipoprotein; D016753:Interleukin-10