title: Chemokine CXCL10 promotes atherogenesis by modulating the local balance of effector and regulatory T cells.
abstract: BACKGROUND
  Studies to define the overall contribution of lymphocytes to lesion formation in atherosclerosis-susceptible mice have demonstrated relatively subtle effects; the use of lymphocyte-deficient mice, however, compromises both the effector and regulatory arms of the immune system. Here, we tested the hypothesis that deletion of CXCL10 (IP-10), a chemokine specific for effector T cells that has been localized within atherosclerotic lesions, would significantly inhibit atherogenesis.
  
  
  RESULTS
  Compound deficient Apoe(-/-)/Cxcl10(-/-) mice fed a Western-style diet for either 6 or 12 weeks demonstrated significant reductions in atherogenesis as compared with Apoe(-/-) controls, as assessed by both aortic en face and cross-sectional analyses. Immunohistochemical studies revealed a decrease in the accumulation of CD4+ T cells, whereas quantitative polymerase chain reaction analysis of lesion-rich aortic arches demonstrated a marked reduction in mRNA for CXCR3, the CXCL10 chemokine receptor. Although overall T-cell accumulation was diminished significantly, we found evidence to suggest that regulatory T-cell (Treg) numbers and activity were enhanced, as assessed by increased message for the Treg-specific marker Foxp3, as well as increases in immunostaining for the Treg-associated cytokines interleukin-10 and transforming growth factor-beta1. We also documented naturally occurring Treg cells in human atherosclerotic lesions.
  
  
  CONCLUSIONS
  We provide novel evidence for a functional role for the effector T-cell chemoattractant CXCL10 in atherosclerotic lesion formation by modulating the local balance of the effector and regulatory arms of the immune system.
authors: Center for Immunology & Inflammatory Diseases, Massachusetts General Hospital, Charlestown, MA 02129, USA.
authors: Eric A
authors: EA
authors: Heller
authors: Emerson
authors: E
authors: Liu
authors: Andrew M
authors: AM
authors: Tager
authors: Qian
authors: Q
authors: Yuan
authors: Alexander Y
authors: AY
authors: Lin
authors: Neil
authors: N
authors: Ahluwalia
authors: Krister
authors: K
authors: Jones
authors: Stephanie L
authors: SL
authors: Koehn
authors: Vincent M
authors: VM
authors: Lok
authors: Elena
authors: E
authors: Aikawa
authors: Kathryn J
authors: KJ
authors: Moore
authors: Andrew D
authors: AD
authors: Luster
authors: Robert E
authors: RE
authors: Gerszten