CCR5+ T-bet+ FoxP3+ Effector CD4 T Cells Drive Atherosclerosis

Jie Li, Sara McArdle, Amin Gholami, Takayuki Kimura, Dennis Wolf, Teresa Gerhardt, Jacqueline Miller, Christian Weber, Klaus Ley

Research output: Contribution to journalArticlepeer-review

74 Scopus citations


Rationale: CD4 T cells are involved in the pathogenesis of atherosclerosis, but atherosclerosis-specific CD4 T cells have not been described. Moreover, the chemokine(s) that regulates T-cell trafficking to the atherosclerotic lesions is also unknown. Objective: In Apoe -/- mice with mature atherosclerotic lesions (5 months of high fat diet), we find that most aortic T cells express CCR5 and interferon-γ with a unique combination of cell surface markers (CD4 + CD25 - CD44 hi CD62L lo) and transcription factors (FoxP3 + T-bet +). We call these cells CCR5Teff. We investigated the role of CCR5 in regulating T-cell homing to the atherosclerotic aorta and the functionality of the CCR5Teff cells. Methods and Results: CCR5Teff cells are exclusively found in the aorta and para-aortic lymph nodes of Apoe -/- mice. They do not suppress T-cell proliferation in vitro and are less potent than regulatory T cells at inhibiting cytokine secretion. Blocking or knocking out CCR5 or its ligand CCL5 significantly blocks T-cell homing to atherosclerotic aortas. Transcriptomic analysis shows that CCR5Teff cells are more similar to effector T cells than to regulatory T cells. They secrete interferon-γ, interleukin-2, interleukin-10, and tumor necrosis factor. Adoptive transfer of these CCR5Teff cells significantly increases atherosclerosis. Conclusions: CCR5 is specifically needed for CD4 T-cell homing to the atherosclerotic plaques. CCR5 + CD4 T cells express an unusual combination of transcription factors, FoxP3 and T-bet. Although CCR5Teff express FoxP3, we showed that they are not regulatory and adoptive transfer of these cells exacerbates atherosclerosis.

Original languageEnglish (US)
Pages (from-to)1540-1552
Number of pages13
JournalCirculation research
Issue number10
StatePublished - May 13 2016
Externally publishedYes


  • CCR5 protein, mouse
  • Ccl5 protein, mouse
  • Treg cells
  • atherosclerosis
  • chemokines
  • inflammation
  • vascular diseases

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine


Dive into the research topics of 'CCR5+ T-bet+ FoxP3+ Effector CD4 T Cells Drive Atherosclerosis'. Together they form a unique fingerprint.

Cite this