Alloantigen-enhanced accumulation of CCR5+ 'effector' regulatory T cells in the gravid uterus.
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.
Kallikourdis
Marinos
M
Laboratory of Molecular Biology, Medical Research Council, Hills Road, Cambridge CB2 2QH, United Kingdom.
Andersen
Kristian G
KG
Welch
Katie A
KA
Betz
Alexander G
AG
D000818:Animals; D054407:Chemokine CCL4; D018925:Chemokines / Q000235:genetics; D019742:Chemokines, CC / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D007108:Immune Tolerance; D007519:Isoantigens / Q000378:metabolism*; D008213:Lymphocyte Activation; D008297:Male; D008431:Maternal-Fetal Exchange / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018448:Models, Immunological; D011247:Pregnancy; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D019713:Receptors, CCR5 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000276:immunology*; D014599:Uterus / Q000166:cytology / Q000276:immunology*
C066507:CCL4 protein, human; D054407:Chemokine CCL4; D018925:Chemokines; D019742:Chemokines, CC; D007519:Isoantigens; D012333:RNA, Messenger; D019713:Receptors, CCR5