Chemokine receptors (CCRs) have been shown to regulate T cell migration and
differentiation as well as the establishment of Th1/Th2 bias. Furthermore,
T cells and T cell products are essential to trophoblast development. Thus
, postulating that chemokines as well as their receptors may be expressed b
y trophoblast to move T cells into an interaction with the fete-placental u
nit, we examined whether CCRs are expressed during the early stages of ecto
placental cone (EPC) formation. For this, murine EPC-derived trophoblast we
re examined for their ability to express CCRs constitutively or inducible b
y interferon-gamma (IFN-gamma). Immunofluorescence experiments on EPC-deriv
ed trophoblast cells showed that CCR3, CXCR4 and CCR5 are significantly exp
ressed. IFN-gamma accelerated the mobilization of intracellular pools of CC
R molecules during early cell culture periods (2-6 h) and, in most cases, i
ncreased their expression on EPC-derived trophoblast cells. CCR activity co
uld be detected in the culture supernatants of these cells, inversely propo
rtional to cell surface expression, suggesting the existence of rapid endoc
ytosis and recycling mechanisms. This finding indicates that the level of i
ntracellular CCRs may partly be determined in the extracellular matrix, an
event that could play an important role towards neutralization of specific
T cell/trophoblast interactions during early stages of pregnancy and protec
t the fetus against harmful maternal immune responses. (C) 2001 Elsevier Sc
ience Ireland Ltd. All rights reserved.