摘要
目的:探讨CD4分子D1区CC’环模拟肽802-2在人Th1和Th2细胞对同种异体抗原刺激的体外增殖反应的调整效应。方法:从健康人外周血中通过免疫磁化分离出CD4^+T淋巴细胞作为反应细胞,HLA不相合的EBV转化的人B淋巴细胞照射后作为刺激细胞,分别在IL-2和IL-12或IL-4的存在下诱生Th1细胞或Th2细胞,观察在不同时间点和不同浓度下加入802-2后,Th1细胞或Th2细胞对同种异体抗原的刺激体外增殖反应的抑制效应。结果:加入终浓度为200μmol/L的802-2,Th1/Th2细胞的增殖反应明显被抑制(P<0.01),但在培养72h后再加入802-2,则这种抑制效应明显减弱。802-2终浓度为50μmol/L以下组与100μmol/L以上组的抑制效应差异有显著性意义(P<0.01),但终浓度为25μmol/L组与50μmol/L组、100μmol/L组与200μmol/L组的抑制效应差异无显著性意义。结论:终浓度≥100μmol/L的802-2能明显减低Th1和Th2细胞对同种异体抗原的增殖反应,显示其在抑制移植物抗宿主病发病过程中的CD4^+T淋巴细胞的反应有潜在的治疗价值。推测802-2拮抗了在同种异体抗原刺激下,CD4/MHC Ⅱ类分子/抗原肽/TCR复合体形成后CD4-D1区与CD4-D1区的相互作用,阻碍了复合体的多聚化。
Objective:To study the efficacy of D1-CC loop of human CD4 peptide 802-2 in modulating allogene-ic responses of both Th1 and Th2 cells in vitro. Method:Primary polarization of Th cells were performed by stimulating purified CD4+ cells from healthy donors by immunomagnetic separation with irradiated EBV transformed B cells (EBV-B) obtained from unrelated, HLA mismatched donors in the presence of Thl (IL-2 + IL-12) or Th2 (IL-2 + IL-4) polarizing cytokines. The effects of 802-2 in different concentration and time points reduced the proliferation of both Thl and Th2 cells in response to allogeneic antigen were therefore tested. Result: The presence of 802-2 significantly reduced the proliferation of both Thl and Th2 cells in allogeneic stimulation. Delaying exposure to 802-2 by more than 72 hours after allogeneic stimulation substantially reduced or eliminated its ability to inhibit proliferation .The final concentration of 802-2 in 100μM and 200μmol showed more significant inhibition of alloresponse of Th cells than in 25μmol and 50μmol(P <0. 01), however, had no significant different inhibition between 25μmol and 50μmol , 100μmol and 200μmol( P >0. 05). Conclusion:The final concentration of 802-2 more than 100μM can significantly reduced the proliferation of both Th1 and Th2 cells. These combined results suggest the potential therapeutic value of 802 - 2 for inhabition of CD4+ T cell allogeneic response in GVHD. The peptide antagonizes the CD4-D1/CD4-D1 interaction following CD4/MHC class-II /antigen/TCR complex formation and inhibits multimerization of complex during allostimulation.
出处
《临床血液学杂志》
CAS
2003年第5期225-229,共5页
Journal of Clinical Hematology
