The embryo expresses paternal Ags foreign to the mother and therefore has been viewed as an allograft. It has been shown that anergic T cells generated by blocking of the CD28/B7 costimulatory pathway with anti B7-1 and anti B7-2 mAbs can be transferred as suppresser cells to prevent allograft rejection. Little is known, however, about the in vivo function of anti-B7-treated T cells after their transfer into abortion-prone mice in the maintenance of materno-fetal tolerance. In the present study, abortion-prone CBA/J females mated with DBA/2 males were administered anti-B7-1 and anti-B7-2 mAbs on day 4 of gestation (murine implantation window). The anti-B7-treated T cells subsequently were adoptively transferred into abortion-prone CBA/J mice. We demonstrated that costimulation blockade with anti-B7 mAbs at the time of implantation resulted in altered allogeneic T cell response and overcame increased maternal rejection to the fetus in the CBA/J DBA/2 system. The transferred anti-B7-treated T cells appeared to be regulatory, decreasing responsiveness and generating clonal deviation in maternal recipient T cells. The transferred CFSE-labeled T cells were found to reside in the spleen and uterine draining lymph nodes, and a few were localized to the materno-fetal interface of the maternal recipient. Our findings suggest that the anti-B7-treated T cells not only function as potent suppresser cells, but also exert an immunoregulatory effect on the maternal recipient T cells, which cosuppresses maternal rejection to the fetus. This procedure might be considered potentially useful for fetal survival when used as an immunotherapy for human recurrent spontaneous abortion.

Intervention in B7 (CD80/CD86)/B7-ligand (CD28/CTLA-4) pathways is an effective way of preventing unwanted immune responses, such as allograft rejection. Pregnancy maintenance represents maternal tolerance to the fetal allograft, which is accompanied by a type 2 helper cell (Th2) bias at the maternalfetal interface. Here, the costimulatory signal of CD86 was selectively blocked, and that of CD80 was kept unimpaired by administration of anti-murine CD86 monoclonal antibody at the early gestational stage in abortion-prone CBA/J3DBA/2 matings and normal pregnant CBA/J3BALB/c matings. It was demonstrated that in vivo blockade of CD86 costimulation could suppress maternal immune attack to the fetus by shifting cytokines from Th1 predominance to Th2 bias at the maternal-fetal interface, and expanding peripheral CD41CD251 regulatory T cells, which play an important role in the development and maintenance of maternal-fetal tolerance. Furthermore, the expression of CD28 and its ligands CD80/CD86 on peripheral lymphocytes was down-regulated, whereas that of CTLA-4 was up-regulated, which might facilitate the suppressive effect of CD4+CD25- regulatory T cells on the alloreactive T cells. The maternal-fetal immunotolerance induced by CD86 blockade decreased fetal resorption in CBA/J3DBA/2 matings, but did not affect normal pregnant CBA/J3BALB/c matings. These results suggest that selective blockade of CD86 costimulation leads to maternal immune tolerance to embryo antigen, and might contribute to a rational immunoregulatory regimen for recurrent spontaneous abortion.

More than 70% of decidual lymphocytes are NK cells characterized by CD56brightCD16- phenotype, but the mechanisms by which these NK cells are recruited in the decidua are still almost unrevealed. In this study, we first analyzed the transcription of 18 chemokine receptors in the first-trimester decidual CD56brightCD16- NK cells. Among these receptors, CXCR4 and CXCR3 were found highly transcribed, and the expression of CXCR4 was verified in most of the decidual CD56brightCD16-NK cells by flow cytometry. The first-trimester human trophoblasts were found expressing CXCL12/stromal cell-derived factor 1, the specific ligand of CXCR4, by way of in situ hybridization and immunohistochemistry. The primary cultured trophoblast cells were also found to secrete stromal cell-derived factor 1-spontaneously, and its concentration was 384.6-90.7pg/ml after the trophoblast cells had been cultured for 60 h. All of the ligands for CXCR3 were below the minimal detectable concentration when trophoblast cells were cultured for up to 48 h. Both recombinant human SDF-1-and supernatants of the cultured trophoblast cells exhibited chemotactic activity on decidual CD56brightCD16- NK cells. Our findings suggest that human first-trimester trophoblast cells produce CXCL12, which in turn chemoattracts decidual CD56brightCD16- NK cells. This activity could contribute to the recruitment mechanism of decidual lymphocytes, especially CD56brightCD16-NK cells, in decidua, and may be used at a local level to modulate the immune milieu at the materno-fetal interface.

BACKGROUND: Chemokines play an important role in the pathogenesis of endometriosis. In the present study, the transcription of 18 chemokine receptors in eutopic endometrium and ectopic tissue with endometriosis was first analysed by RT–PCR. Dioxin, an air pollutant, and estrogen are reported to be associated with endometriosis. The regulatory mechanisms of dioxin and estrogen in the expression of CXCR1/IL-8 in the corresponding cells will help in elucidating roles of the chemokine in the aetiology of endometriosis. METHODS AND RESULTS: CXCR1, a type of chemokine receptor, was over-expressed in endometriotic tissue. The high translation of the receptor and its ligand, interleukin (IL-8), in endometriotic tissue was then demonstrated by immunochemistry. Estradiol and 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin (TCDD) alone inhibited expression of CXCR1, whereas the combination of estradiol with TCDD up-regulated the expression. TCDD promoted IL-8 secretion by human pelvic mesothelial cells (HPMC), and 17 -estradiol magnified the stimulatory effect. Both 17-estradiol and TCDD alone inhibited IL-8 secretion of U937 (a cell line of monocyte), but combination of 17-stradiol and TCDD had no further inhibitory effect. The co-culture of endometrial stromal cells (ESC) with HPMC produced more IL-8 than respective or total production of either of the cells alone, and estradiol played a synergistic stimulatory role with TCDD in IL-8 secretion of the co-culture. Interaction of HPMC and the monocytes significantly stimulated IL-8 secretion, suggesting a main resource of IL-8 in peritoneal cavity with endometriosis. TCDD promoted IL-8 secretion by HPMC-U937 co-culture, but exerted a contrary effect for IL-8 secretion when combined with estradiol. CONCLUSION: Estradiol and TCDD in the peritoneal cavity can lead to a persistent and serious inflammation, which gives a new insight into the interactions of estrogen and TCDD in endometriosis.

Objective: To compare the effects of treatment of tubal pregnancy (TP)and its following second pregnancy by intratubal methotrexate injection (IMI) alone and combination of IMI with Chinese herbal medicine. Metlmds: Thirty-five patients sudferiug from unruptured TP were divided into two groups at random, to the 19 patients in the treated group, the treatment of combined IMI with Ectopic Pregnancy decoction No.2 (EP2, a traditional Chinese medical decoction) was applied, and to the other 16 patients in the control group, IMI alone was applied for control. Sexum concentrations of h-man chorionic gonadotro-pin (HCG), size of the gestational sac, existent time of fetal cardiac beat and peritoneal fluid were measured before and after treatment. And hysterosalpingography were performed 6 months after pnding the treatment to verify the presence of tubal obstruction and the condition of relapse. Results: The treat-ment of all the 35 women was suceessful. The recovery duration of serum β-HCG, disappeerance duration of TP sac and existent time of peritoneal fluid in the treated group were 20.04-7.8 days, 1.24-0.7 months and 10.74-2.9 days respectively, which were significantly different from those in the control group (24.4 4-8.1 days, 3.64-1.7 months and 19.14-3.2 days respectively(P＜0.05, P＜0.01 and P＜0.05 respec-β-tivdy), but the existent time of fetal cardiac beat in the two groups (8.84-1.9 days vs 9.0 4-1.3 days) was not significantly different (P~0.05). The post-treatment oviduct obstructive rate in the two groups was 10.5% and 43.8% respectively, that in the treatment group was less significant (P＜0.05). The relapse rate of EP in the treatment group was insignificantly different from that in the control group (5.3% vs 18.8%,P＜0.05).usion: The two therapies (IMI alone and IMI combined with EP2) could obtain e-qual efficacy in curing TP. Compared with IMI alone, the combined therapy appears to have the effects of accelerating the resorption of gestational sac and peritoneal fluid, improving the patency of fallopian tube and ameliorating the cirolm~tance of pregnancy, which is hvorable to improvement of the re-pregnancy rate and reduction of the re-occurrence of ectopic pregnancy as well as to the enhancement of the effect of IMI in killing trophocytes. But there is not enough proof to show the potency of EP2 in killing embryo.