title: Differential effects of regulatory T cells on the initiation and regression of atherosclerosis.
abstract: OBJECTIVE
  Regulatory T cells (Tregs) play an important role in the regulation of T cell-mediated immune responses through suppression of T cell proliferation and cytokine production. In atherosclerosis, a chronic autoimmune-like disease, an imbalance between pro-inflammatory cells (Th1/Th2) and anti-inflammatory cells (Tregs) exists. Therefore, increased Treg numbers may be beneficial for patients suffering from atherosclerosis. In the present study, we determined the effect of a vast expansion of Tregs on the initiation and regression of well-established lesions.
  
  
  RESULTS
  For in vivo Treg expansion, LDL receptor deficient (LDLr(-/-)) mice received repeated intraperitoneal injections of a complex of IL-2 and anti-IL-2 mAb. This resulted in a 10-fold increase in CD4(+)CD25(hi)Foxp3(+) T cells, which potently suppressed effector T cells ex vivo. During initial atherosclerosis, IL-2 complex treatment of LDLr(-/-) mice fed a Western-type diet reduced atherosclerotic lesion formation by 39%. The effect on pre-existing lesions was assessed by combining IL-2 complex treatment with a vigorous lowering of blood lipid levels in LDLr(-/-) mice. This did not induce regression of atherosclerosis, but significantly enhanced lesion stability.
  
  
  CONCLUSIONS
  Our data show differential roles for Tregs during atherosclerosis: Tregs suppress inflammatory responses and attenuate initial atherosclerosis development, while during regression Tregs can improve stabilization of the atherosclerotic lesions.
authors.affiliation: Division of Biopharmaceutics, Leiden University, Leiden, The Netherlands. a.c.foks@lacdr.leidenuniv.nl
authors.forename: A C
authors.initials: AC
authors.lastname: Foks
authors.forename: V
authors.initials: V
authors.lastname: Frodermann
authors.forename: M
authors.initials: M
authors.lastname: ter Borg
authors.forename: K L L
authors.initials: KL
authors.lastname: Habets
authors.forename: I
authors.initials: I
authors.lastname: Bot
authors.forename: Y
authors.initials: Y
authors.lastname: Zhao
authors.forename: M
authors.initials: M
authors.lastname: van Eck
authors.forename: Th J C
authors.initials: TJ
authors.lastname: van Berkel
authors.forename: J
authors.initials: J
authors.lastname: Kuiper
authors.forename: G H M
authors.initials: GH
authors.lastname: van Puijvelde
mesh_terms: D000818:Animals; D050197:Atherosclerosis / Q000378:metabolism*; D015551:Autoimmunity / Q000235:genetics; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology; D051858:Forkhead Transcription Factors / Q000096:biosynthesis; D005786:Gene Expression Regulation; D007249:Inflammation / Q000473:pathology; D007376:Interleukin-2 / Q000235:genetics; D053645:Interleukin-2 Receptor alpha Subunit / Q000096:biosynthesis; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D050378:T-Lymphocytes, Regulatory / Q000166:cytology* / Q000378:metabolism; D018417:Th1 Cells / Q000166:cytology; D018418:Th2 Cells / Q000166:cytology; D016896:Treatment Outcome
chemical_list: D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D007376:Interleukin-2; D053645:Interleukin-2 Receptor alpha Subunit