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李大金, Xiu-Li Wang, Da-Jin Li*, Min-Min Yuan, Min Yu, Xiao-Ying Yao
Journal of Reproductive Immunology 63(2004)97-110,-0001,():
-1年11月30日
The vaccine directed against human chorionic gonadotropin (hCG) has previously undergone clinical test demonstrating the feasibility of the approach in preventing pregnancy in women. Some individuals, however, did not response adequately despite employing highly immunogenic bacterial toxoids as carriers. In this study, we investigated the potential of three copies of C3d as a new molecular adjuvant to enhance the immunogenicity of hCGβ protein antigen. The antibody response to the hCGβ-C3d3 fusion protein immunization was compared with those resulting from immunization with the hCGβ alone and the hCGβ plus CFA/IFA either in BALB/c mice or in C57BL/6J mice. Our results showed that the fusion of C3d3 to hCGβ protein antigen resulted in a significant elevation of the serum anti-hCGβ antibody level in the two mouse strains and the antibodies were capable of effectively neutralizing the bioactivity of hCG. The immunization with C3d3 as a molecular adjuvant favored Th2 bias of immune response. The immunity-enhancing effect of the C3d3 was 10-fold (initial) and 20–32-fold (booster) greater than CFA/IFA. These findings indicated that fusion of C3d3 to hCGβ, as a means of harnessing the adjuvant potential of the innate immune system, may improve immunogenicity of the hCGβ contraceptive vaccine, which is useful to produce a cost-effective vaccine and for the less-responsive population.
hCGβ, Protein antigen, C3d3, Molecular adjuvant, Humoral immunity
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李大金, Dajin Li*, Xiaoxi Sun, Chaojing Li, Lirong Cai, Yi Meng
Journal of Reproductive Immunology 54(2002)81-92,-0001,():
-1年11月30日
Objectie: to evaluate the effects on fertility by immunization with anti-idiotypic antibodies to porcine zona pellucida (PZP) antigen. Method: anti-idiotypic antibodies (Ab2) were produced in New Zealand rabbits immunized with 17D3 monoclonal antibodies (mAbs) (IgG, Ab1) to PZP antigen. The antisera were first passed through immuno-affinity chromatography column linked to normal mouse IgG so as to remove the antibody bound to normal mouse IgG The passing elute was then purified by immuno-affinity chromatography using 17D3 mAbs to get the Ab2. Female BALB/c mice, 5-week-old, were grouped and immunized with the Ab2, PZP antigen, target antigen of the Ab1 and normal rabbit IgG, respectively. The treated female mice were mated with male BALB/c mice and sacrificed at gestation day 10. Analyses included ELISA measurement of anti-ZP antibody titer, fetal number determination and evaluation of ovarian histomorphology. Results: the Ab2 appeared as a single protein band by SDS-PAGE. Shown by a competitive inhibition ELISA, the Ab2 specifically bound to the variable region of the 17D3 Ab1. Compared with controls, the female mice immunized with Ab2 showed a decreased pregnancy rate and a statistically significant reduction in fetal numbers. Histological examination of ovaries demonstrated that Ab2 exposure interfered less with follicular development than did exposure to PZP. Conclusion: immunization of female mice with Ab2 to PZP mAbs suppresses fertility and fetal numbers with minimal ovarian pathology.
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李大金, Ying-Li Shi, , Xue-Zhen Luo, Xiao-Yong Zhu, Ke-Qin Hua, Ying Zhu and Da-Jin Li
Human Reproduction Vol.21, No.4 pp. 870-879, 2006,-0001,():
-1年11月30日
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.
endometriosis, 17β-estradiol, interleukin-8, TCDD, co-culture
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李大金, Yu Huang, Xiao-Yong Zhu, Mei-Rong Du, Xia Wu, Ming-Yan Wang and Da-Jin Li
Human Reproduction Vol.21, No.4 pp. 1083-1091, 2006,-0001,():
-1年11月30日
The aim of this study was to investigate whether CXCL16/CXCR6, a newly identified chemokine pair, is expressed in first-trimester human placenta and whether they affect the trophoblast cell biology, since we have found CXCR6 highly transcribed in first-trimester human trophoblast cells previously. METHODS: We analysed the transcription and translation of CXCR6 and CXCL16 in purified first-trimester human trophoblast cells by real-time RT-PCR and immunochemical staining. We then examined the kinetic secretion of CXCL16 in the supernatant of primary-cultured trophoblast by enzyme-linked immunosorbent assay. We further investigated effects of CXCL16 on the proliferation and invasion of trophoblast cells in vitro. RESULTS: We found the chemokine pair CXCL16/CXCR6 was transcribed and translated in first-trimester trophoblast cells and JAR line. In addition, the primary-cultured trophoblasts secreted CXCL16 spontaneously and continuously in 100-h culture. Treating trophoblasts with CXCL16 induced marked proliferation and invasion in vitro. CONCLUSION: The findings from this study have demonstrated for the first time that CXCR6 and CXCL16 are co-expressed by first-trimester human trophoblast cells and stimulate their proliferation and invasion in an autocrine/paracrine manner. It suggests that CXCL16 plays important roles in human extravillous cytotrophoblast invasion and placentation.
Chemokine, chemokine receptor, invasion, proliferation, trophoblast cell
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李大金, Xiao-Yong Zhu, Yue-Hua Zhou, Ming-Yan Wang, Li-Ping Jin, Min-Min Yuan, and Da-Jin Li
BIOLOGY OF REPRODUCTION 72, 338-345 (2005),-0001,():
-1年11月30日
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.
Cytokines, embryo, immunology, pregnancy
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