Th1-and Th2-type lymphokine-assisted induction and release of chemokine receptors from primary human trophoblast cells

Chemokine receptors (CCRs) have been demonstrated to facilitate the entry o f HIV in different cell types of infected individuals, including CD4(+) T c ells and dendritic cells. The natural or inducible expression of CCRs on tr ophoblast cells could provide a valid mechanism for the ill utero transmiss ion of HIV from mother to fetus. Because of the rapid turnover of these rec eptors, ive attempted to define the natural and inducible expression of sur face CCR3 and CXCR4 on primary human trophoblasts during short periods of c ell culture. In the absence of any external stimulus the expression of CCR3 and CXCR4 varied from 1% to 24%. Kinetic experiments show that the levels of both CCR3 and CXCR4 reach a peak of expression after 6 h of culture, whe reas by 24 h they have almost disappeared. In the presence of IFN-gamma, CC R3 is showing an increasing pattern of expression after 4 h of incubation, reaching highest levels after 24 h of culture, whereas CXCR4 is kept at low er levels as compared with nontreated cells. Furthermore, in the presence o f IL-4, CCR3 expression declines from 2 to 8 h of culture to increase again at 24 h, where 50% of the cell population is expressing the receptors, Und er the IL-4 stimulus, CXCR4 shows a peak of expression at 8 h of culture. A n interesting feature of this study is that we were able to detect soluble CCR activity in the culture supernatants of trophoblast cells, which follow ed an inverse pattern of this of surface expression. Thus, the inability of many laboratories to detect high levels of CCRs in placentae of HIV infect ed mothers may be due on these fast turnover of these receptors, which by t he assaying time have either been released in the culture medium or been in ternalized to the cell. Human Immunology 61, 651-657 (2000). (C) American S ociety for Histocompatibility and Immunogenetics, 2000. Published by Elsevi er Science Inc.