Alloantigen-enhanced accumulation of CCR5+ 'effector' regulatory T cells in the gravid uterus

Proc Natl Acad Sci U S A. 2007 Jan 9;104(2):594-9. doi: 10.1073/pnas.0604268104. Epub 2006 Dec 29.


Regulatory T cells play an essential role in preventing fetal rejection by the maternal immune system. Here we show that, based on the expression of CCR5, regulatory T cells can be divided into a highly suppressive CCR5+ and a far less suppressive CCR5- subpopulation, suggesting that the former represent the effector arm of regulatory T cells. Although regulatory T cells from CCR5-/- gene deletion mutants still suppress, they are less effective mediators of maternal-fetal tolerance. The accumulation of CCR5+ regulatory T cells at this site appears to be enhanced by alloantigen. This finding is in stark contrast to the systemic expansion of regulatory T cells during pregnancy, which appears to be alloantigen-independent. The fact that CCR5+ regulatory T cells preferentially accumulate in the gravid uterus and that expression of CCR5 on regulatory T cells can be induced by activation lead us to propose that CCR5 is responsible for the accumulation of those regulatory T cells that have been activated by paternal antigens.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Chemokine CCL4
  • Chemokines / genetics
  • Chemokines, CC / metabolism
  • Female
  • Gene Expression
  • Immune Tolerance
  • Isoantigens / metabolism*
  • Lymphocyte Activation
  • Male
  • Maternal-Fetal Exchange / immunology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Models, Immunological
  • Pregnancy
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Receptors, CCR5 / deficiency
  • Receptors, CCR5 / genetics
  • Receptors, CCR5 / metabolism*
  • T-Lymphocytes, Regulatory / cytology
  • T-Lymphocytes, Regulatory / immunology*
  • Uterus / cytology
  • Uterus / immunology*


  • CCL4 protein, human
  • Chemokine CCL4
  • Chemokines
  • Chemokines, CC
  • Isoantigens
  • RNA, Messenger
  • Receptors, CCR5